Stereochemical Aspects of Acid‐Catalyzed Cyclopropane Ring‐Opening Reactions. A Stereospecific Pathway to Crinosterol and Brassicasterol

Abstract

SummaryIt is shown that the acid-catalyzed ring-opening of the two diastereoisomeric 23,24-methylenecholesterols 3 and 5 on treatment with gaseous HCl in acetic acid leads stereospecifically to the naturally occurring crinosterol (4) and brassicasterol (6), respectively (Scheme I ) . This isomerization can be viewed as a biomimetic model of an in vivo methylation process of the type already known in plant sterol metabolism (cJ: cycloeucalenol+ obtusifoliol, 1 4 2). The synthetic application of this method provides a convenient labelling of sterol side chains for tracer experiments. The mechanistic features of the reaction with respect to its particular stereospecificity are discussed.Introduction. -Are sterols containing a cyclopropane ring moiety metabolic dead ends or do they represent biosynthetic intermediates? This question has become relevant with the recent isolation of many such sterols [ 11. Lederer originally postulated [2] that cyclopropanes may serve as intermediates for methyl groups through a biochemical reductive opening, but he rejected this consideration on the basis of negative experimental results. However in vivo C-alkylation by isomerization of a cyclopropane intermediate to a methylated product (with an additional double bond) has been shown experimentally to be operative in plant sterol metabolism [3]. Thus cycloeucalenol (1) seems to play a key role in the biosynthesis of phytosterols since enzymatic opening of the three-membered ring leads to the A'-isomer obtusi-

Identification of crinosterol from astigamatid mites

“…This cycloether (340 mg, 0.82 mmol) was hydrolyzed to give crinosterol (258 mg, 0.65 mmol) in 79% yield. All physicochemical properties are identical with those reported previously (Lang and Djerassi, 1982) …”

Sterols from Mytilidae Show Anti-Aging and Neuroprotective Effects via Anti-Oxidative Activity

“…This fraction was mainly composed of steroids (70%). SF was further purified by reversed-phase high performance liquid chromatography (HPLC) to yield four compounds, the structures of which were determined as cholesterol [ 18 , 19 ], brassicasterol [ 20 , 21 ], crinosterol [ 20 , 22 ], and 24-methylenecholesterol [ 23 ] ( Figure 1 A) based on their spectroscopic characteristics and comparison of spectroscopic data with those in the literature. Quantitative analysis showed that the percentages of CHOL, brassicasterol, crinosterol, and 24-methylenecholesterol in the SF were 27%, 19%, 12%, and 12%, respectively.…”

Steroids from the starfish Euretaster insignis: a novel group of sulphated 3β,21-dihydroxysteroids

“…(20R)-24-Methyfenecholest-5-ene-3f3,2 18 (20R,22E)-24-Methylcholest-22-ene-3f3,2 1 -diyl diacetate (4a)diacetute, m / z 440 (M' -AcOH, 41%), 425 (13), 397 (30), 337 (15), 315 (loo), 257 (42), and 255 (43); 6, 0.71 (s, 18-H3), 0.82 (s, 19-H,), 0.87 and 0.88 (overlapping doublets, 26-and 27-H,), 0.93 (d, J 7 , 28-H3), 2.00 and 2.02 (each s, CH,CO), 3.92 and 4.18 (each dd, J 10.5 and 8, and 10.5 and 3.5, together 21-H,), 4.69 (m, 3a-H), 5.10 (dd, J 16 and 8.7,22-H), and 5.26 (dd, J 16 and (20R)-Cholestane-3P,2 1 -diyl diacetate (la)-diacetate, m/z 488 ( M + , 41%), 428 (99, 317 (99, and 215 (100); 8, 0.68 (s, 18-H3), 0.82 (s, 19-H,), 0.86 (d, J, 7,26-and 27-H3), 2.02 and 2.05 (each s, CH,CO), 4.02 and 4.19 (each dd, J 10.5 and 6, and 10.5 and 3, together 21-H2) and 4.69 (m, 3a-H). (dd, J 10.5 and 6.5,21-H), 4.60 (m, 3a-H), and 5.37 (d, J 5,6-H); 6, (2a)-diacetate 0.82 (s, I8-H3), 3.90 (dd, J 10.…”