Organocuprate-mediated methods for the stereospecific introduction of steroid side chains at C-20

Abstract

The reactions of organocuprates with various A17(20)-unsaturated steroid substrates leads to the stereocontrolled introduction of the side chain onto the steroid nucleus to give either desired C-20 epimer. The reaction of an £,-A17(2°)-16-keto steroid with lithium diisohexylcuprate leads to -face attack, giving exclusively a product having the "natural" 20/? chirality. This product was then converted to cholesterol. The reactions of either the E-17,20)-16a-pivalyloxy or the corresponding 16/3-pivaloyloxy steroid with lithium isohexylcyanocuprate each proceeded in a regio-and stereocontrolled manner. The former (16a) compound gave exclusively the "unnatural" 20S chirality while the latter (16/3) compound gave exclusively the "natural" 20.R chirality. The 20S compound was converted to 20-epicholesterol, and similarly, the 20R compound was converted to cholesterol. A result complementary to that of the pivalates ensued from the £-A17(20)-16a-jV-phenylcarbamoyl steroid, which was converted by the action of a presumed internal mixed cuprate to a compound having 20fi chirality.

The Truth about False Unicorn (Chamaelirium luteum): Total Synthesis of 23R,24S‐Chiograsterol B Defines the Structure and Stereochemistry of the Major Saponins from this Medicinal Herb

“…[33] Initially, conjugate addition to 21 was investigated, as previous reports indicated creation of the correct stereochemistry at both C-17 and C-20. [34] It was hoped that with the hindered steroidal enone 1,4-addition might predominate with a range of different nucleophiles. Thus, enone 21 was treated with Grignard reagent 24 a in the presence of AlCl 3 (to suppress g-adduct formation), [35] but yielded mixtures of 1,2-and 1,4-addition products.…”

Synthesis of the Reported Structure of trans-Africanan-1α-ol

“…This became important, because Dibal reduction followed by Wolff-Kishner deoxygenation 11 delivered a product tertiary alcohol 1 that was not congruent with the reported natural product. Although many of the structures of the africanane sesquiterpenes have been confirmed by total synthesis, 12,13 there is at least one other example 12g of synthesis uncovering an incorrect structural assignment.…”

Total Synthesis of Candicanoside A, a Potent Antitumor Saponin with a Rearranged Steroid Side Chain

“…A 20‐OH group in the steroids could facilitate the functionalization of the proximal 18‐Me group 9. Therefore, compound 7 , with a hydroxy group at C20( R )10 and 3,5‐cyclo‐6‐methoxy protection of the 3‐hydroxy‐5,6‐ene functionality in the AB ring, was prepared from alkene 6 by hydroboration and oxidation; compound 6 was obtained conveniently from 5 in three steps (62 %) 11. Irradiation of 7 in the presence of iodine and DIB in cyclohexane with a 300‐W tungsten lamp for approximately 30 min, followed immediately by oxidation with PCC, provided the desired ketone 8 with an iodo substituent at C18 in a satisfactory yield (50 %) 9.…”