Lipase-catalyzed resolution of anti-6-substituted 1,3-dioxepan-5-ols

Abstract

Abstract-Several anti-6-substituted 1,3-dioxepan-5-ols were kinetically resolved using an immobilized lipase (Amano PS-C II) in toluene in the presence of vinyl acetate at 30°C. This approach provided, in some cases, the alcohol and the acetate in high enantiomeric purity, depending on the nature of the substituent (R = N 3 , SePh, I, OBn) and the acetal group (unsubstituted or dimethyl). The role of the size of substituents is also discussed. Enantiopure anti-6-substituted 1,3-dioxepan-5-ols are useful building blocks.

Biocatalytic routes to anti-viral agents and their synthetic intermediates

“…211 Noto and co-workers analogously used immobilised Amano PS lipase (a Burkholderia cepacia (BCL) preparation) to resolve dioxepanes 145 and 146 at laboratory scale (Scheme 31B). 212 Bare ABT 138 itself also provides for an attractive target for biocatalytic production due to its high solubility and the presence of two adjacent chiral centres in a small molecule. Lye and co-workers developed a two-step enzymatic cascade for the synthesis of ABT.…”

“…Although constituting a very attractive cascade, no enantiomeric and/or diastereomeric purity was reported, the transaminase Scheme 30 Synthesis of nelfinavir from suitably protected 3-aminobutane-1,2,4-triol (ABT) as described by Uchida et al (I), 208 Cho and co-workers (II) 209 and Borer et al 210 Scheme 31 Resolution of protected ABT derivatives 143 (A) 211 and 145/ 146 (B). 212 PPL: porcine pancreas lipase, PFL: Amano AK lipase (P. fluorescens), BCL: Amano PS lipase (Burkholderia cepacia) and BCL-C II: BCL immobilised on ceramic instead of diatomite.…”