Regioselective biotransformations of dinitriles using Rhodococcus sp. AJ270

A variety of dinitriles have been hydrolysed selectively under very mild conditions using Rhodococcus sp. AJ270. Aliphatic dinitriles NC[CH2](n)CN 1 undergo regioselective hydrolysis to give the mono acids 2 with up to 4 methylenes between the nitrile functions while those with n > 4 give the diacids 3 in good yield. Dinitriles NC[CH2](n)X[CH2](n)CN 4 bearing an ether or sulfide linkage are efficiently transformed into the mono acids 5 when an oxygen is placed beta, gamma or delta to the cyano group or a beta- or gamma-sulfur is present. Hydrolysis of N,N-bis(2-cyanoethyl)anilines 4h-j takes place slowly affording exclusively the monoacids 5h-j while the monocyano amides 5o-p are obtained as the sole isolable product from rapid hydrolysis of the corresponding N,N-bis(2-cyanomethyl)butylamine 40 and N,N-bis(3-cyanopropyl)butylamine 4p. Higher homologues of arylimino- and butylimino-dinitriles are inert to enzymatic hydrolysis. A variety of other aliphatic dinitriles have been converted readily into mono acids in good to excellent yields except for o-phenylenediacetonitrile which gives o-phenylenediacetamide as the major product. The title organism also effects the hydrolysis of aromatic dinitriles with regiocontrol such as m- and p-dicyanobenzenes, but not the ortho-substituted analogue. The scope and limitations of this enzymatic process have been systematically studied and the mechanism of regioselective hydrolysis has been discussed in terms of a chelation-deactivation effect.