Steroidal cyclobutanones, III. The Synthesis and Stereochemistry of 3‐Spiro‐5α‐cholestane Derivatives with Three‐, Four‐, and Five‐membered Carbon Rings—A Double Cine Substitution in Spiro‐α,α‐dichlorocyclobutan‐3‐ones

Abstract

Diastereomeric [(3S)‐5α]‐ and [(3R)‐5α]‐2′,2′‐dichlorospiro‐[cholestane‐3,1′‐cyclobutan]‐3′‐ones (1 and 2), prepared by cycloaddition reaction of dichloroketene with 3‐methylene‐5α‐cholestane, served as starting material for the synthesis of the related spirane derivatives. Thus, the synthesis of spiro‐cyclopentane (3–6), spirocyclobutane (9, 11, 13, 17–20) and spirocyclopropane steroids (12, 14, 15) is described. The sterically dependent reaction of spiro‐α,α‐dichlorocyclobutan‐3‐ones with an excess of sodium methanolate in methanol is reported. Thus, the reaction of 1 with sodium methanolate gives 9, the product of the double cine substitution, while the corresponding reaction of compound 2, which is sterically more hindered for similar nucleophilic attack, gives mainly the spirocyclopropane 12. The stereochemistry of the spiro compounds is assigned on the basis of 1H‐ and 13C‐NMR spectra.

Ring Expansion of Cyclobutylmethylcarbenium Ions to Cyclopentane or Cyclopentene Derivatives and Metal-Promoted Analogous Rearrangements

“…In research on linked donor−acceptor systems designed to test the effect of bridge configuration on the dynamics of long-range intramolecular electron transfer processes, polycycle 552 was synthesized as a single regioisomer in nearly quantitative yield from its precursor, whereas adamantane derivative 553 was synthesized in 90% yield from the corresponding α,α-dichlorobutanone . 5α-Cholestane-3-spirocyclopentanone 554 was synthesized in 97% yield from the precursor 5α-2′,2′-dichlorospiro[cholestane-3,1′-cyclobutan]-3′-one via the described diazomethane ring enlargement …”

Steroids: reactions and partial synthesis

“…The synthesis and rearrangement of the diastereoisomeric dichlorospiro(cholestane-3,1 '-cyclobutan)-3'-ones (68) and ( 70) have been described. 95 The differing steric hindrance experienced by the two chloroketones was reflected in their reactions with sodium methoxide. Thus (68) gave the dimethyl ether (69) whereas (70) gave the spirocyclopropane (71).…”

“…The synthesis of blattellastanoside A (94), a steroid glucoside which is the aggregation pheromone of the German cockroach, has been re~0rted.l~' A number of 3P-glycoside sulfates have been preparedlgO whilst analogues of the dimeric cephalostatin antibiotics have been synthesizedl'l from hecogenin. The stereoselective synthesis of 7P-phenyl and 7P-methyl cholesterol from 7-oxocholesteryl acetate has been reported.lg2 Some potentially hypocholesterolemic 15-keto steroids (95) have been prepared from d i ~s g e n i n . ~' ~ Intermediates in the biosynthetic modification of the sterol side chain in the conversion of cholesterol to pregnenolone have been prepared .194*195 The action of inhibitors of sterol biosynthesis including compounds with fluorinated side chains has been examined.lg6 Some of these compounds affect HMG CoA reductase activity.…”