Bacterial Preparation of Enantiopure Unactivated Aziridine-2-carboxamides and Their Transformation into Enantiopure Nonnatural Amino Acids and vic-Diamines

Abstract

[reaction: see text] Enantiopure (1R,2S)-1-benzyl- and 1-arylaziridine-2-carboxamides were obtained by kinetic resolution of their racemates by Rhodococcus rhodochrous IFO 15564 catalyzed hydrolysis. Several regio- and enantioselective nucleophilic ring openings of (1R,2S)-1-benzylaziridine-2-carboxamide or its LAH-reduced product led to a series of enantiopure products, such as O-methyl-l-serine and some vicinal diamines.

Spoxazomicin D and Oxachelin C, Potent Neuroprotective Carboxamides from the Appalachian Coal Fire-Associated Isolate Streptomyces sp. RM-14-6

“…While key 2D NMR experiments including HMBC and COSY cannot differentiate between 1 and 1a (Figure 2), the distinct 13 C NMR chemical shift of CH 2 -9 ( δ C 70.2) implicates the presence of a CH 2 -O ( 1 ) rather than a CH 2 -N ( 1a ) connection. Consistent with this, a survey of the spectral features for other reported aziridine-containing natural products 1 reveals the 13 C chemical shift of the aziridine ring carbons to be in the range δ C 33–44 ppm across well-established comparators (including azinomycins, 39 mitomycins, 40,41 albomitomycins/isomitomycins, 41 mitiromycins, 42 ficellomycin, 43 FR-66979, 44 and other closely related structures 45 ). In contrast, the 13 C NMR chemical shift of the putative aziridine carbons of 19 – 22 are ~70 ppm.…”

Rhodococcus as a Versatile Biocatalyst in Organic Synthesis

“…Malononitriles are α, α-substituted dinitriles that form malonic diamides and malonic acid monoamides upon incubation with whole-cells of R. rhodochrous IFO 15564 [150]. Next to that, cyanohydrins (α-hydroxy nitriles) were also successfully hydrolyzed, leading to enantiopure α-hydroxy carboxylic acids like the pharmaceutical intermediate ( R )-chloromandelic acid on gram-scale [151] as was a large variety of aminonitriles ranging from α-aryl-, α-alkyl-substituted glycine nitriles [152,153,154] to aziridine-2-carbonitriles [155], azetidine-2-carbonitriles, and 4-oxoazetidine-2-carbonitriles [156,157].…”

Synthesis of Nβ-Substituted α,β-Diamino Acids via Stereoselective N-Michael Additions to a Chiral Bicyclic Dehydroalanine

“…7 Many synthetic approaches have been developed to obtain both DAP enantiomers in a stereoselective manner. [8][9][10] Other important Nβ-substituted α,β-diamino acids are some analogous of histidine, such as β-(1-pyrazolyl)alanine or β-(1-triazolyl)alanine, that involve the substitution of imidazole ring by pyrazole or triazole, respectively, and have been used for diabetes treatment. [11][12][13] These compounds have been accessed by N-nucleophilic displacement of β-haloalanine derivatives, 14 by ring-opening of aziridines, 15 lactones 16 or cyclic sulfamidates, 17 or by chemoenzymatic synthesis using N-Michael addition on dehydroalanines (Dha).…”