Synthesis of Quaternary‐Carbon‐Containing and Functionalized Enantiopure Pentanecarboxylic Acids from Biocatalytic Desymmetrization of meso‐Cyclopentane‐1,3‐Dicarboxamides

Abstract

Catalyzed by Rhodococcus erythropolis AJ270, a nitrile hydratase-amidase containing microbial whole-cell catalyst under mild conditions, enantioselective desymmetrizations of meso-cyclopentane-1,3-dicarbonitriles and cyclopentane-1,3-dicarboxamides were studied. Although the nitrile hydratase was found to exhibit high enzymatic activity, but low 1R enantioselectivity toward dinitriles, a number of 2,2-unsymmetrically substituted meso-cyclopentane-1,3-dicarboxamide substrates were converted by the 1S enantioselective amidase into quaternary carbon-bearing enantiopure (1S,2R,3R)-3-carbamoylcyclopentanecarboxylic acids in yields up to 94 %. The application of the method was demonstrated by convenient and practical transformations of the resulting (1S,2R,3R)-2-allyl-3-carbamoylcyclopentanecarboxylic acid derivatives into functionalized cyclopentane-fused δ-lactam and δ-lactone compounds.

Enantioselective Biotransformations of Nitriles in Organic Synthesis

“…In comparison with N-heterocyclic diamides 76, the biotransformations of meso cyclopentane-1,3-dicarboxamides 78 proceed more sluggishly because of the steric hindrance of the two substituents at the 2-position. 46 However, the reaction is accelerated effectively when the biocatalyst loading is doubled. Diamides 78a−e, in which the larger group is oriented trans to the amido groups, are biotransformed into, afetr esterification, enantiopure (1S,2S,3R)-3-carbamoylcyclopentanecarboxylic acid benzyl esters 79a−e in excellent yields (Figure 15).…”

“…In comparison with N-heterocyclic diamides 76 , the biotransformations of meso cyclopentane-1,3-dicarboxamides 78 proceed more sluggishly because of the steric hindrance of the two substituents at the 2-position . However, the reaction is accelerated effectively when the biocatalyst loading is doubled.…”

Rhodococcus as a Versatile Biocatalyst in Organic Synthesis

“…Multiple examples of dinitriles were also applied: incubation of R. erythropolis AJ270 cells with meso - c -pentane-1,3-dinitriles yielded optically active amide-products in high yields [149]. Via an amidase-catalyzed kinetic resolution step and following treatment with CH 2 N 2 , monocyano amides were resolved into (-)-amide and (-)-ester.…”

Biocatalytic Desymmetrization of Dinitriles in Organic Synthesis

“…值得一提的是, 酶催 化 2,5-二酰胺基四氢吡咯 42a 的去对称化反应效率非常 高, 可以 94%的产率一锅得到 19 g 对映体纯产物 2-羧基 -5-酰胺基四氢吡咯(43h). 随后, 该课题 组 [29] 又以相 似的方法研究内消旋 1,3-环戊二腈和 同时王梅祥课题组还展示了生物转化方法在合成 具有潜在药物活性化合物上的应用 [28,29]…”