Effective High‐Pressure Cleavage of Sterically Hindered Steroid Esters

Abstract

A simple and effective method to deprotect of sterically hindered steroid esters is described. Deprotection was carried out in MeOH in the presence of a catalytic amount of Et 3 N under high-pressure conditions. Enzymatic, anionite, and high-pressure methods are compared.

Asymmetric 1,3-dipolar cycloadditions of chiral carboxyloyl nitrile oxides to cycloalkenes

“…4,5,6,7,8,isoxazole-3-carboxylic acid (1 0 R)-8 0 -phenylmenthyl ester 9b. Yield: 48%; HRMS-ESI: calcd for C 25 H 35 O 3 N (M+Na) + 420.25146; found, 420.25102; LSIMS (+) NBA 8 kV (%) 420 (M+Na) + (100), 398 (M+H) + (7), 215 (20), 170 (31), 119 (18), 105 (40); IR (film) 2926,2855,1730,1710,1582,1495,1455,1390,1333,1266,1232,1127,984,939,764,701 …”

“…3a,4,5,6,7,7a-Hexahydro-1,2-benzisoxazole-3-carboxylic acid N,N-dicyclohexyl-10-sulfamoyl-(2R)-isoborneol ester 8c. Yield: 43%; HRMS-ESI: calcd for C 30 H 49 O 5 N 2 S (M+H) + 549.33622; found, 549.33779; LSIMS (+) NBA 8 kV (%) 549 (M+H) + (18), 380 (74), 246 (14), 228 (26), 180 (43), 135 (100), 83 (47); IR (film) 3424,2934,2854,1718,1449,1394,1323,1258,1222,1165,1143,1079,1048,981,892,774,576 80, 158.44, 82.29, 79.61, 57.38, 53.37, 49.35, 49.17, 44.55, 43,67, 39.39, 32.50, 30.25, 27.06, 26.46, 26.26, 25.74, 25.27, 24.82, 21.49, 20.45, 19.72. 4.1.8.…”

Mild alkaline hydrolysis of hindered esters in non-aqueous solution

“…[21][22][23][24][25] These include, among others, the use of potassium tert-butoxide in DMSO, [21][22] the use of a KOH complex in the presence of a phase-transfer catalyst, 23 and the transesterification of sterically-hindered steroid esters to methyl esters in MeOH/Et3N under high-pressure conditions. 24 Cleavage of tert-butyl benzoates has been attempted with NaH in DMF or, alternatively, with KOH/THF/crown ethers at high temperature. 25 The tert-butyl moiety is widely used as a valuable protecting group for acids and alcohols in organic synthesis, since tert-butyl esters are remarkably stable to basic hydrolysis, but labile to acid hydrolysis.…”

High pressure in organic chemistry on the way to miniaturization

“…174 Chiral macrocyclic tetraamines derived from a-amino acids have been synthesized in good yields at 10 kbar. 175 These macrocycles were used for a study of metal complexation 176,177 The Jurczak group studied the implementation of high pressure in many other reactions like the cleavage of sterically hindered steroid esters 178 and the synthesis of crown ethers, cryptands, 179,180 azacoronands, 181 and herbicides. 182 Matsumoto et al have studied the influence of pressure on several heterocyclic organic reactions.…”