| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Total cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol and coronary heart disease in Scotland Hargreaves, A. D., R. L. Logan, et al. (1991), Bmj 303(6804): 678-81. Abstract: OBJECTIVE--To investigate long term changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations and in measures of other risk factors for coronary heart disease and to assess their importance for the development of coronary heart disease in Scottish men. DESIGN--Longitudinal study entailing follow up in 1988-9 of men investigated during a study in 1976. SETTING--Edinburgh, Scotland. SUBJECTS--107 men from Edinburgh who had taken part in a comparative study of risk factors for heart disease with Swedish men in 1976 when aged 40. INTERVENTION--The men were invited to attend a follow up clinic in 1988-9 for measurement of cholesterol concentrations and other risk factor measurements. Eighty three attended and 24 refused to or could not attend. MAIN OUTCOME MEASURES--Changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations, body weight, weight to height index, prevalence of smoking, and alcohol intake; number of coronary artery disease events. RESULTS--Mean serum total cholesterol concentration increased over the 12 years mainly due to an increase in the low density lipoprotein cholesterol fraction (from 3.53 (SD 0.09) to 4.56 (0.11) mmol/l) despite a reduction in high density lipoprotein cholesterol concentration. Body weight and weight to height index increased. Fewer men smoked more than 15 cigarettes/day in 1988-9 than in 1976. Blood pressure remained stable and fasting triglyceride concentrations did not change. The frequency of corneal arcus doubled. Alcohol consumption decreased significantly. Eleven men developed clinical coronary heart disease. High low density lipoprotein and low high density lipoprotein cholesterol concentrations in 1976, but not total cholesterol concentration, significantly predicted coronary heart disease (p = 0.05). Almost all of the men who developed coronary heart disease were smokers (91% v 53%, p less than 0.05). CONCLUSION--Over 12 years the lipid profile deteriorated significantly in this healthy cohort of young men. Smoking, a low high density lipoprotein concentration and a raised low density lipoprotein concentration were all associated with coronary heart disease in middle aged Scottish men, whereas there was no association for total cholesterol concentration. The findings have implications for screening programmes. |
| Total cholesterol, total triglycerides, and cholesterol distribution among lipoproteins as predictors of atherosclerosis in selected lines of Japanese quail Hammad, S. M., H. S. Siegel, et al. (1998), Comp Biochem Physiol A Mol Integr Physiol 119(2): 485-92. Abstract: The proportions of plasma high and low density lipoprotein cholesterol have been linked to inherited tendency for atherosclerosis in humans. Studies were conducted with Japanese quail males from lines genetically selected for high and low TC and a randombred (unselected) control line that were fed 0.0 or 0.5% cholesterol for 12 weeks. Atherosclerotic plaques were more severe in the high than in the low line quail and in those fed cholesterol compared to non-cholesterol-fed quail. Serum TG, TC, VLDLC, LDLC, and HDLC were also higher in the high than in the low line quail and in cholesterol-fed vs. non-cholesterol-fed quail. Significant interactions indicated that TC and LDLC concentrations were more affected by dietary cholesterol in the high line than in the low line. The low line quail maintained higher HDLC and lower LDLC than the high line. Regression and correlation analyses revealed that although VLDLC, LDLC, and TC were significant predictors of atherosclerosis in the high line birds, the TC/HDLC ratio was a better predictor in the low line. The Japanese quail lines used herein represent useful experimental models for studies of genetic differences in atherosclerosis in humans. |
| Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study Lemieux, I., B. Lamarche, et al. (2001), Arch Intern Med 161(22): 2685-92. Abstract: BACKGROUND: Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratios are used to predict ischemic heart disease risk. There is, however, no consensus on which of these 2 indices is superior. The objective of the present study was to present evidence that the LDL-C/HDL-C ratio may underestimate ischemic heart disease risk in overweight hyperinsulinemic patients with high triglyceride (TG)-low HDL-C dyslipidemia. METHODS: A total of 2103 middle-aged men in whom measurements of the metabolic profile were performed in the fasting state were recruited from 7 suburbs of the Quebec metropolitan area. RESULTS: The relationship of LDL-C/HDL-C to TC/HDL-C ratios was examined among men in the Quebec Cardiovascular Study classified into tertiles of fasting TG levels. For any given LDL-C/HDL-C ratio, the TC/HDL-C ratio was higher among men in the top TG tertile (>168 mg/dL >1.9 mmol/L) than in men in the first and second TG tertiles. Adjustment of the TC/HDL-C ratio for LDL-C/HDL-C by covariance analysis generated significant differences in average TC/HDL-C ratios among TG tertiles (P<.001). Greater differences in features of the insulin resistance syndrome (insulinemia, apolipoprotein B, and LDL size) were noted across tertiles of the TC/HDL-C ratio than tertiles of the LDL-C/HDL-C ratio. CONCLUSION: Variation in the TC/HDL-C ratio may be associated with more substantial alterations in metabolic indices predictive of ischemic heart disease risk and related to the insulin resistance syndrome than variation in the LDL-C/HDL-C ratio. |
| Total discrimination of peritoneal malignant ascites from cirrhosis- and hepatocarcinoma-associated ascites by assays of ascitic cholesterol and lactate dehydrogenase Castaldo, G., G. Oriani, et al. (1994), Clin Chem 40(3): 478-83. Abstract: No laboratory test completely distinguishes malignant ascites (MA) from ascites associated with cirrhosis and (or) hepatocellular carcinoma (A/C-HC). Ascitic cytology is highly specific but has a diagnostic sensitivity of only 40-60%. We determined 11 ascitic analytes and cytology in 58 patients with cirrhosis, 15 with hepatocellular carcinoma, and 21 with MA (10 ovarian cancers, 4 mesotheliomas, 6 gastrointestinal neoplasias, 1 leukemia). Ascitic total protein, cholesterol, pseudouridine, and lactate dehydrogenase (LD), and the ascitic:serum ratios of total protein and of LD showed the most significant differences between the two groups of patients. Stepwise multiple linear discriminant analysis (applying the Wilks' lambda criterion) of several variables, corroborated by the "jack-knife" reallocation procedure, showed that the ascitic cholesterol and ascitic LD association correctly identified 100% of MA and A/C-HC; cytology had a diagnostic specificity of 100%, but identified only 48% of MA. This association may represent a primary tool for the discrimination of ascites of unknown origin, particularly in the presence of negative cytology findings. |
| Total error assessment of five methods for cholesterol screening Miller, W. G., J. M. McKenney, et al. (1993), Clin Chem 39(2): 297-304. Abstract: We report the accuracy, imprecision, total analytical errors, and patient misclassification errors for cholesterol measured from capillary whole blood, venous whole blood, and venous plasma samples by five devices used in public cholesterol screening environments: Reflotron, Vision, Ektachem DT-60, QuickRead, and Liposcan. None of the methods met the National Cholesterol Education Program (NCEP) performance recommendations of 3% CV with 3% bias. The Vision and Reflotron methods used with venous samples gave individual results with total errors consistent with a combined CV and bias in the 4-5% range; capillary blood samples had total errors > 5% (combined CV and bias criteria). The DT-60 performance was near the 5% total error criterion for capillary samples and was > 5% for venous samples. Misclassification of individuals into desirable or referral groups for venous samples was as great as 5.1% for the DT-60, 5.7% for the Vision, and 7.1% for the Reflotron. Misclassifications for capillary blood samples were as great as 6.7%, 18.3%, and 14.1% for DT-60, Vision, and Reflotron, respectively. The QuickRead and Liposcan results were substantially poorer than those obtained by the other methods. |
| Total error evaluation of Roche direct HDL-cholesterol reagent and calibrator across 31 lot combinations: a 2-year experience Cobbaert, C. M. and T. K. Luderer (2000), Clin Chem 46(1): 133-4. |
| Total parenteral nutrition containing medium- vs. long-chain triglyceride emulsions elevates plasma cholesterol concentrations in rats Ney, D. M., H. Yang, et al. (1993), J Nutr 123(5): 883-92. Abstract: Male Fischer 344 rats (235-246 g) were fed for 6-14 d by intravenous or intragastric infusion with total parenteral nutrition (TPN) solutions providing 40 or 65% of nonprotein energy as fat from long-chain triglyceride (LCT) or a 3:1 admixture of medium-chain triglyceride (MCT) and LCT emulsions. In three separate experiments, plasma cholesterol concentrations were significantly greater (24-32%) with intravenous infusion of TPN solutions containing MCT-LCT rather than LCT. Plasma cholesterol concentrations in rats were not significantly different with intragastric infusion of TPN solutions containing MCT-LCT rather than LCT. Hepatic total lipid and triglyceride concentrations were not significantly different. Hepatic total cholesterol and esterified cholesterol concentrations were significantly lower in animals given 65% of energy from MCT-LCT rather than LCT emulsions (main effects, two-way ANOVA). The concentration of individual hepatic acyl-CoA esters reflected the fatty acid profiles of the lipid emulsions infused. Total hepatic acyl-CoA concentrations suggested differences in utilization of acyl-CoA esters with intravenous infusion of MCT-LCT rather than LCT and were consistent with rapid oxidation of MCT. These data demonstrate that MCT-LCT elevates plasma cholesterol concentrations compared with LCT emulsions with intravenous, but not with intragastric, infusion of TPN solutions in rats. |
| Total parenteral nutrition stimulates hepatic cholesterol synthesis in the rat Hajri, T., J. Ferezou, et al. (1995), Biochim Biophys Acta 1258(2): 188-94. Abstract: Cholesterol synthesis was studied in parenterally fed rats, as compared to orally fed rats with or without saline infusion. Conditions of total parenteral nutrition (TPN) involved the intravenous infusion of a nutritive mixture containing 20% Intralipid as the lipid source (50% of non-protein energy) at the continuous rate of 2 ml per h, for five days. In rats maintained in isotopic steady state by daily injections of 3Hcholesterol, isotope dilution indicated that the endogenous plasma cholesterol input was significantly higher (+15%, P < 0.05) in TPN than in orally fed rats, which suggested a slight stimulation of whole body cholesterogenesis. Cholesterol synthesis was assessed in TPN and orally fed rats by the in vivo incorporation of 1,2-13C- and 1-14Cacetate into hepatic and intestinal sterols, and by the activity of HMG-CoA reductase in microsomes isolated from liver and small intestine. Both methods demonstrated that TPN markedly stimulated the hepatic cholesterol synthesis, since the radioactivity of liver sterols was 6- to 10-fold higher, and the activity of HMG-CoA reductase 5-fold higher, in TPN than in orally fed rats. Despite the weight reduction of the small intestine, by about 20% after TPN, the incorporation of exogenous 14Cacetate into intestinal sterols was similar in TPN and orally fed rats. As the liver and intestine are the main organs responsible for the appearance of endogenous cholesterol in plasma, it may be concluded that the increased endogenous plasma cholesterol input was mainly due to a strong stimulation of hepatic cholesterol synthesis in TPN rats. |
| Total plasma cholesterol levels of rats are increased following only three sessions of tailshock Brennan, F. X., Jr., R. F. Job, et al. (1992), Life Sci 50(13): 945-50. Abstract: Male Sprague-Dawley rats were maintained for three weeks on one of three different diets. Two of the diets were high-cholesterol, high-fat, while the third was standard laboratory chow. Animals from each group were then given either daily 2 hr sessions of tailshock for three days, or left in their home cage. Blood samples were taken from all subjects prior to stress, and again immediately after the third stress session. Sera were separated and analyzed for total plasma cholesterol. Results indicate that total plasma cholesterol was increased in the stressed animals maintained on standard lab chow. Stressed animals in the two high cholesterol diet groups showed no cholesterol increase relative to their respective dietary controls. |
| Total protein content of human gallbladder bile: relation to cholesterol gallstone disease and effects of treatment with bile acids and aspirin Sahlin, S. (1996), Eur J Surg 162(6): 463-9. Abstract: OBJECTIVE: To measure the total protein content of gallbladder bile, and assess how treatment with aspirin and the gallstone solvents chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) affects the biliary protein concentration. DESIGN: Prospective study. SETTING: Teaching hospital, Sweden. SUBJECTS: 102 Consecutive patients undergoing cholecystectomy for cholesterol gallstones (n = 73) or adenomyomas or cholesterolosis in the gallbladder wall (n = 29). Thirty of the patients with gallstones were treated with CDCA, UDCA or aspirin. INTERVENTIONS: Aspiration of bile from the gallbladder during operation. MAIN OUTCOME MEASURES: Protein content, and correlations between protein content and biliary lipids, cholesterol saturation and crystals, and concentrations of individual bile acids. RESULTS: There were no differences in total protein content among the groups except for the UDCA treated group, which had significantly less protein 2.1 (0.5) g/l compared with 6.1 (0.5) for untreated gallstones, 5.8 (0.9) for those treated with CDCA, 6.8 (1.2) for those treated with aspirin and 7.3 (0.7) for those with no gallstones). There were no differences between bile with and without crystals. There was a positive correlation between the protein content and biliary cholesterol concentration and saturation. Aspirin did not influence the total protein content in the bile. CONCLUSIONS: The total protein concentration in gallbladder bile was similar in patients with and without cholesterol crystals, which might indicate that the total protein content in bile does not influence formation of cholesterol crystals and consequently not the formation of gallstones. Patients treated with UDCA were the only group that had significantly less protein than the other groups, which indicates that the mode of action of UDCA is different from that of CDCA. |
| Total serum cholesterol and cholesterol lipoprotein fractions in random sample of Warsaw population Chotkowska, E., B. Jasinski, et al. (1999), Pol Arch Med Wewn 102(5): 945-54. Abstract: The aim of the study was to evaluate the level of lipid risk factors in a random sample of Warsaw population aged 35-64 years, 764 men and 775 women, were screened within framework of the Pol-MONICA Warsaw Study. The lipids were determined by enzymatic methods in laboratory controlled by CDC Lipid Standardization Program in Atlanta. In the screened sample the observed levels of total cholesterol (5.76 +/- 1.01 and 5.68 +/- 1.03 mmol/l respectively in men and in women) and LDL cholesterol (3.67 +/- 0.90 and 3.56 +/- 0.94 mmol/l respectively) were rather high what can indicate on rather high coronary risk of Warsaw population. On the other hand the high mean level of HDL cholesterol (1.36 +/- 0.36 and 1.53 +/- 0.35 mmol/l respectively) and its subfractions HDL2 (0.24 in men and 0.39 mmol/l in women) as well as HDL3 (1.12 and 1.14 mmol/l respectively) observed in this sample can decrease this global risk. The compared mean level of cholesterol in lipoprotein fractions in the group of investigated persons with and without clinical manifestations of coronary heart disease confirm the observed in the other studies the higher mean levels of total cholesterol and LDL cholesterol in persons with coronary heart disease. |
| Total serum cholesterol and suicidality in anorexia nervosa Favaro, A., L. Caregaro, et al. (2004), Psychosom Med 66(4): 548-52. Abstract: OBJECTIVE: No published study has evaluated the relationship between serum cholesterol and suicidality in anorexia nervosa (AN). AIMS: To assess psychiatric and nutritional correlates of serum cholesterol in a sample of AN patients. METHODS: Serum cholesterol and nutritional status were evaluated in a sample of 74 AN patients, before starting any type of refeeding. All subjects underwent a structured clinical interview and completed the Hopkins Symptom Checklist. RESULTS: Subjects who reported previous suicide attempts, impulsive self-injurious behavior, or current suicidal ideation showed significantly lower cholesterol levels than subjects without suicidality. Cholesterol levels were negatively correlated with the severity of depressive symptoms in all the patients with the exception of those with recurrent binge eating. A multivariate analysis showed that the relationships between cholesterol levels and suicidal behavior and ideation do not seem to be affected by the nutritional and metabolic factors considered in the study. CONCLUSIONS: Notwithstanding the influence of important metabolic factors affecting cholesterolemia in AN, our research tends to confirm previous studies that have found an association between low cholesterol levels and suicidality. |
| Total serum cholesterol and triglycerides and risk of breast cancer: a prospective study of 24,329 Norwegian women Vatten, L. J. and O. P. Foss (1990), Cancer Res 50(8): 2341-6. Abstract: The association between total serum cholesterol and triglycerides and the incidence rate of breast cancer has been examined in 242 incident cases of breast cancer that developed among 24,329 Norwegian women during 11-14 years of follow-up. At the time of lipid measurement they were between 35 and 51 years of age. There was an inverse relation between serum cholesterol and risk of breast cancer which was confined to women diagnosed before the age of 51. The incidence rate ratio was 0.53 (95% confidence limits, 0.32 and 0.88) for women in the highest quartile of serum cholesterol (mean = 8.52 mM = 329 mg/100 ml) compared to women in the lowest quartile (mean = 5.28 mM = 204 mg/100 ml), and the relation displayed a negative trend over quartiles of cholesterol (chi 2 for trend = 3.94, P = 0.05). No association with cholesterol was found among cases diagnosed during the initial 2 years of follow-up, whereas a strong inverse relation was observed among cases that were diagnosed during the following 4 years (chi 2 trend = 12.6, P less than 0.001). For serum triglycerides there was an overall negative, but not statistically significant, association with breast cancer incidence, which was weakened after further adjustment for body mass index and serum cholesterol. The lack of information on reproductive factors associated with breast cancer risk is a limitation of this study, since potential confounding with the results cannot be excluded. We conclude that there is an inverse relation between serum cholesterol and breast cancer risk among women diagnosed before the age of 51 years. The findings indicate that the negative association cannot easily be attributed to a preclinical effect of the cancer. |
| Total serum cholesterol in children 8-15 years of age Kotesovec, F. and J. Sevcik (1992), Cesk Pediatr 47(2): 85-8. Abstract: The authors evaluated the difference in the health status of two groups of boys and girls aged 8-15 years, a total of 1037 children. The larger group, 790 children is from Teplice and the other group, a total of 347 children from Roudnice nad Labem. The authors discuss the total serum cholesterol level in the two groups. They provide information on mean serum cholesterol levels in children of comparable age and the significance of differences in relation to age and sex. The assembled values made it possible to calculate percentile values at the 90th and 95th percentile level for children of both areas and thus to examine and evaluate larger groups of children incl. their relatives and to detect critical total cholesterol levels calling for treatment and intervention. |
| Total serum cholesterol in postmenopausal women: prediction of future levels through a simple measurement Hetland, M. L., J. Haarbo, et al. (1993), Ugeskr Laeger 155(7): 478-81. |
| Total serum cholesterol in relation to psychological correlates in parasuicide Garland, M., D. Hickey, et al. (2000), Br J Psychiatry 177: 77-83. Abstract: BACKGROUND: Low cholesterol may act as a peripheral marker for parasuicide. AIMS: To examine the relationship between total serum cholesterol and psychological parameters in parasuicide. METHOD: Total serum cholesterol and self-rated scores for impulsivity, depression and suicidal intent were measured in 100 consecutive patients following parasuicide, pair-matched with normal and psychiatric control groups. RESULTS: Backward, stepwise multiple regression analysis revealed a significantly lower mean cholesterol in the parasuicide population (P < 0.01). Across all groups there was an independent significant (P < 0.01) negative correlation between cholesterol and self-reported scores of impulsivity. No correlation existed between cholesterol and scores for depression or suicidal intent. CONCLUSIONS: The data confirm previous reports of low cholesterol in parasuicide. This is the first reported investigation of the construct of impulsivity in relation to cholesterol. We hypothesise that the reported increased mortality in populations with low cholesterol may derive from increased suicide and accident rates consequent on increased tendencies to impulsivity in these populations. |
| Total serum cholesterol level, violent criminal offences, suicidal behavior, mortality and the appearance of conduct disorder in Finnish male criminal offenders with antisocial personality disorder Repo-Tiihonen, E., P. Halonen, et al. (2002), Eur Arch Psychiatry Clin Neurosci 252(1): 8-11. Abstract: Associations between low total serum cholesterol (TC) levels and antisocial personality disorder (ASPD), violent and suicidal behavior have been found. We investigated the associations between TC levels, violent and suicidal behavior, age of onset of the conduct disorder (CD) and the age of death among 250 Finnish male criminal offenders with ASPD. The CD had begun before the age of 10 two times more often in non-violent criminal offenders who had lower than median TC levels. The violent criminal offenders having lower than median TC levels were seven times more likely to die before the median age of death in the study material. The violent offenders having lower than median TC levels were eight times more likely to die of unnatural causes. The mean TC level of these male offenders with ASPD was lower than that of the general Finnish male population. Low TC levels are associated with childhood onset type of the CD, and premature and unnatural mortality among male offenders with ASPD. The TC level seems to be a peripheral marker with prognostic value among boys with conduct disorder and antisocial male offenders. |
| Total serum cholesterol levels and mortality risk as a function of age. A report based on the Framingham data Kronmal, R. A., K. C. Cain, et al. (1993), Arch Intern Med 153(9): 1065-73. Abstract: OBJECTIVE: To evaluate the relationship between serum cholesterol level and all-cause, coronary heart disease (CHD), and non-CHD mortality as a function of age. METHODS: The data source was the biennial examination data from 1948 through 1980 for the 5209 men and women enrolled in the Framingham Heart Study. Age-specific analyses by the Cox proportional hazards regression model were performed of survival subsequent to ages 40, 50, 60, 70, and 80 years for all subjects enrolled and alive at each of the stated ages. Complementary models were studied that used high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, or total cholesterol level as predictors of survival subsequent to the examination at which lipoprotein subfractions were determined (1968) through 1973). RESULTS: The relationship between total cholesterol level and all-cause mortality was positive (ie, higher cholesterol level associated with higher mortality) at age 40 years, negative at age 80 years, and negligible at ages 50 to 70 years. The relationship with CHD mortality was significantly positive at ages 40, 50, and 60 years but attenuated with age until the relationship was positive, but not significant, at age 70 years and negative, but not significant, at age 80 years. Results for the relationship between low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and mortality help explain these findings. Non-CHD mortality was significantly negatively related to cholesterol level for ages 50 years and above. The negative results in the oldest age group for all-cause and CHD morality appeared to be due to a negative relationship with low-density lipoprotein cholesterol levels rather than the protective effect of high high-density lipoprotein cholesterol levels. Similar results from several modified analyses make low cholesterol level due to severe illness an unlikely explanation for our results. CONCLUSIONS: Physicians should be cautious about initiating cholesterol-lowering treatment in men and women above 65 to 70 years of age. Only randomized clinical trials in older people can settle the debate over the efficacy and cost-effectiveness of lipid-lowering interventions for reducing mortality and morbidity in this population. |
| Total serum cholesterol levels in Asians living in New York City: results of a self-referred cholesterol screening Pinnelas, D., R. De La Torre, et al. (1992), N Y State J Med 92(6): 245-9. Abstract: Asians historically have low total cholesterol levels and low incidence of coronary heart disease. In performing a coronary heart disease and total cholesterol screening in New York City's Chinatown, we obtained data supportive of previous studies, which focused on Japanese populations and described the influence of environment on total cholesterol. In the present study, Chinese living in Chinatown have higher levels of total cholesterol than would be expected from studies of Chinese living in Shanghai. For every age group examined, Asian-born Chinese living in Chinatown had higher total cholesterol levels than both urban and rural Chinese in Shanghai. In subjects less than or equal to 30 years of age, urban males in Shanghai had cholesterol levels of 160 +/- 34 mg/dL, compared with 206 +/- 38 mg/dL for Asian-born males in Chinatown. For females in the same age category, cholesterol levels were 162 +/- 35 mg/dL vs 224 +/- 45 mg/dL, respectively. Applying National Cholesterol Education Panel (NCEP) guidelines, the distribution of desirable, borderline-high, and high blood cholesterol levels for the Chinese in Chinatown (41%, 35%, and 23%, respectively) were similar to a group of Caucasians screened (42%, 32%, and 26%) and the group recently used to determine the prevalence of high blood cholesterol in American adults (43%, 30%, and 27%). Studies are needed to stratify the risk of coronary heart disease in other groups that traditionally have a low incidence of coronary heart disease, but which now have adopted Western lifestyles. |
| Total synthesis of ent-cholesterol via a steroid C,D-ring side-chain synthon Jiang, X. and D. F. Covey (2002), J Org Chem 67(14): 4893-900. Abstract: For the first time, one of the two enantiomers of cholesterol (ent-cholesterol) has been synthesized by a synthetic route that starts from a precursor containing the D-ring and entire side chain of cholesterol. As part of the reported synthetic route, a method of general utility for the large scale (>10 g) preparation of each enantiomer of 1 alpha(R*),7a alpha-1-(1,5-dimethylhexyl)-1,2,3,6,7,7a-hexahydro-7a-methyl-5H-inden-5-o ne, C,D ring-side chain synthons that can be used for the synthesis of enantiomers of vitamin D(3), cholesterol, and their analogues was also developed. Using the enantiomer of the C,D-ring side-chain synthon that leads to ent-cholesterol, the A- and B-rings were elaborated from a linear fragment that is sequentially cyclized to form the steroid B- and A-rings. Using this route, ent-cholesterol was prepared in 23 steps from the methyl ester of (1 alpha,5 alpha,6 alpha)-(+/-)-6-methyl-2-oxo-bicyclo3.1.0hexane-1-carboxylic acid in a total yield of 2.6%. |