Lipase-catalyzed deprotection

Scheme 11.3 Lipase-catalyzed polymerization of L-tartaric acid derive cyclic carbonate followed by deprotection of the ketal groups to give chiral, hydroxy functional polycarbonate.

Synthesis of BMY-14802 (228) commenced from pyrimidine derivative 243 which reacted with piperazine 244 to give derivative 245 (Scheme 58) [215, 216]. Reduction of the compound 245 followed by deprotection gave amine 246, which was alkylated with chloride 247 and then subjected to acidic hydrolysis to form ketone 248. Reduction of 248 allowed BMY-14802 (228) to be obtained. Pure enantiomers of 228 were also obtained. To achieve this, the following methods were used resolution of 228 with using reaction with a-phenylethyl isocyanate [217] or lipase-catalyzed acetylation or hydrolysis [218], alkylation of 245 with enantiopure alcohols 249 [219] and microbial reduction [305] or Ru-catalyzed enantioselective hydrogenation [220] of 248. 

An easy preparation of mono-deprotected thioglucopyranosides via a Candica cylindracea lipase-catalyzed selective hydrolysis of a commercially available per-acetylated precursor is described in Figure 3.22 [32], Ethyl 2,3,4-tri-O-acetyl-l-thio-P-D-glucopyranoside and ethyl 2,3,6-tri-O-acetyl-l-thio-p-D-glucopyrano-side were obtained in 100% and 54% isolated yields, respectively. 

A patented synthesis by Doan et al. at GlaxoSmithKline used a Patemo-Buchi photochemical reaction to obtain acetal 33 in 96% yield, as shown in Scheme 8.35 Hydrogenation followed by acid-catalyzed cyclization resulted in a diastereomeric mixture of bis-THF alcohol ( )-ll. Formation of acetate 15, followed by lipase resolution resulted in the formation of the acetyl bis-THF, which was subsequently deprotected to afford the desired product (-)-ll in 98% ee.35... 

Much of the current interest in making simple derivatives of (+ )-castanospermine (239) can be traced to a seminal publication in 1989, which showed that the alkaloid s anti-HIV activity could be increased by as much as twenty times upon esterification (216). Positionally selective acylation procedures usually involve sequential protection, acylation, and deprotection steps e.g. the preparation of esters at the C-6 and C-7 (217) or the C-8 hydroxy groups (218). Also of interest are procedures that take advantage of enzyme-catalyzed transesterification with activated esters, e.g. the use of subtilisin for ester formation at C-1, pancreatic porcine lipase for preferential reaction at C-6 and C-7 (219-221), and cross-linked enzyme crystals (CLECs) of subtilisin for making the potentially valuable antitumor agent 1-0-butanoylcastanospermine (222). A cautionary note was sounded, however, when it was observed that 6-0-acyl castanospermine esters could equilibrate to a mixture of... 

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