Lipase-catalyzed selective protection

Figure 26 Lipase-catalyzed selective protection of primary hydroxyl groups of a dimeric glucal.

The Hep-esters proved to be chemically stable during the removal of the N-terminal Z-, Boc- and the Aloe-group from the dipeptides 21. The selective removal of the Hep-esters was achieved by a lipase-catalyzed hydrolysis. From several enzymes investigated, a biocatalyst isolated from the fungus Rhizopus niveus was superior to the others with respect to substrate tolerance and reaction rate. The enzyme accepts a variety of Boc-, Z- and Aloc-protected dipeptide Hep-esters as substrates and hydrolyzes the ester functions in high yields at pH 7 and 37 °C... 

The target molecule 19 was obtained by lipase-catalyzed heptyl ester cleavage and employing sodium methanolate for the removal of the 0-acetyl groups. In summary, this result showed a set of three base-labile protecting groups (Fmoc, OAc, OHep) to be removable selectively and thus useful for the synthesis of complex glycopeptidic structures. 

In recent years biotransformations have also shown their potential when applied to nucleoside chemistry [7]. This chapter will give several examples that cover the different possibiUties using biocatalysts, especially lipases, in order to synthesize new nucleoside analogs. The chapter will demonstrate some applications of enzymatic acylations and alkoxycarbonylations for the synthesis of new analogs. The utQity of these biocatalytic reactions for selective transformations in nucleosides is noteworthy. In addition, some of these biocatalytic processes can be used not only for protection or activation of hydroxyl groups, but also for enzymatic resolution of racemic mixtures of nucleosides. Moreover, some possibilities with other biocatalysts that can modify bases, such as deaminases [8] or enzymes that catalyze the synthesis of new nucleoside analogs via transglycosylation [9] are also discussed. 

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... 

For some enzymes, such as Pseudomonas sp. lipase (PSL), the liberated acid does not present any problems, but others like CRL are more sensitive and require more protection. For instance, when acetic anhydride is used, the Uberated acetic acid may lead to a decrease of the pH in the micro-environment of the enzyme, thus leading to a depletion of activity and selectivity. The CRL-catalyzed resolution of the bicyclic tetrachloroalcohol shown in Scheme 3.5, using acetic anhydride as acyl donor, initially proceeded with only moderate selectivity (E = 18). Addition of a weak inorganic or (preferably) organic base such as 2,6-lutidine which functions... 

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