Jun-ichi Hayami

Synthesis and reaction of novel 5-deazaflavins with axial chirality at pyrimidine ring moiety

Abstract A series of novel 5-deazaflavin derivatives possessing axial chirality at pyrimidine ring moiety have been prepared to investigate effects of the pyrimidine site on the stereoselective reactions between flavins and substrates. Successful optical resolution of the racemic compounds has been achieved by HPLC method on a chiral stationary phase and a diastereomer formation method. The chiral recognition ability of the 5-deazaflavin enantiomers was investigated in a model reaction of asymmetric intercoenzyme “(net) hydride transfer” reactions.

A new olefin synthesis. Synchronous elimination of nitro and ester groups or nitro and keto groups from .beta.-nitro esters or .beta.-nitro ketones

Synthese de nitriles, esters, cetones et sulfones vinyliques a partir de (chloro-1 nitro-1) ou de (bromo-1 nitro-1) alcanes

Diastereoface differentiating “(net) hydride transfer” in novel 5-deazaflavins modified at pyrimidine ring

Abstract In novel 5-deazaflavin models ( 1 )–( 5 ) where one face of the pyrimidine ring moiety is flanked, “(net) hydride transfer” from BNAH ocurred at mainly C(5) on the face which aligns with the open side of the pyrimidine ring. The degree of diastereoface differentiation depends on the bulkiness of the substituent on phenyl group at N(3). The results revealed that the pyrimidine ring moiety of flavin ring system interacts with the carbamoyl group of BNAH in the transition of the “(net) hydride transfer” reaction. Diastereoface differentiating “(net) hydride abstraction” from the reduced 5-deazaflavin was also investigated.

First example of “diastereotopic face activation” and chiral recognition without metal assistance. A novel 5-deazaflavin enzyme model.

Abstract A chiral 5-deazaflavin 1 with 2-hydroxynaphthyl group at N(3) position of the pyrimidine ring moiety was synthesized. 1 underwent, in the absence of magnesium ion, a “(net) hydride transfer” from BNAH to C(5) almost exclusively on the face where OH group is present. It was also the case with PNPH, and enantioselectivity for PNPH by 1 was higher in the absence of magnesium ion than in its presence. These results indicate that the “diastereotopic face activation” in 1 is operated as well as chiral recognition for PNPH by 1 .

Synthesis and reaction of a new type of 5-deazaflavin with axial and planar chirality

Abstract A new type of 5-deazaflavin derivative with axial and planar chirality was synthesized as a flavoenzyme model. A novel optical resolution gave an enantiomeric pair of the 5-deazaflavins 1a,b . Compounds 1a,b were optically stable and effectively discriminated PNPH enantiomers in a model reaction of intercoenzyme hydrogen transfer.

Stereochemistry of asymmetric “(net) hydride transfer” in an intercoenzyme model reaction system

Abstract X-ray crystal structure analysis revealed the absolute configuration of compound 2 and thus proved the absolute configuration of 5-deazaflavin (+)-1 possessing both axial and planar chirality to be (S). Model reactions of “(net) hydride transfer” between 1 and Me2PNPH enanatiomers revealed that (S)-(+)-1 oxidizes (4S)-Me2PNPH more rapidly than its (4R) isomer and that (R)-(−)-1 oxidizes (4R)-Me2PNPH more rapidly than its (4S) isomer. These results strongly suggest that an enatioselectivity on Me2PNPH by chiral 1 is not solely determined by the availability of C(4) hydrogen but by the “(net) hydride donor-acceptor” interactions involving the interaction between the pyrimidine site of 5-deazaflavin molecule and the carbamoyl group of the NAD(P)H model as the important contributor.