Asymmetric Synthesis and Structure‐Activity Relationship of the Four Stereoisomers of the Antibiotic Amidinomycin Part 1: The Synthesis

Abstract

SummaryThe natural amidinomycin ((W, 35)-14) and its three stereoisomers are synthesized from homochual3-oxocyclopentanecarboxytic acids (la) by asymmetric methods, which are based on an asymmetric reductive amination to produce methyl cis-N-( 1 -phenylethyl)-3-aminocyclopentanecarboxylates (3b) via optically active me thy1 N-( l-phenylethyl)-3-iminocyclopmtane-carboxylates (2b) for the cis-isomers of 14. Optically pure trum-3-aminocyclopentane-carboxylic acids (4a) are obtained from the homochiral keto acids la via asymmetric reductive amination of 3-hydroxyiminocyclopentanecarboxytic acids (Sa) and lead to the tmns-isomers of 14.

1‐(Trifluoromethyl)cyclopent‐3‐enecarboxylic Acid Derivatives: Platforms for Bifunctional Cyclic Trifluoromethyl Building Blocks

“…[29] Therefore 23 was saponified (90 % yield) and the resulting N-benzyl amino acid 24 was treated with thionyl chloride (Scheme 7). [30] The recovered major isomer t-24 (51 % yield) and the N-benzyl lactam 25 (28 % yield) were separated. Hydrolysis of 25 under harsh acidic conditions or with concentrated aqueous sodium hydroxide failed.…”

Rhodium‐Catalyzed 1,4‐Addition of Lithium 2‐Furyltriolborates to Unsaturated Ketones and Esters for Enantioselective Synthesis of γ‐Oxo‐Carboxylic Acids By Oxidation of the Furyl Ring with Ozone

“…Methyl 3‐oxocyclopentanonecarboxylate :23f, 31 Yield: 82 %; 1 H NMR (400 MHz, CDCl 3 ): δ =3.68 (s, 3 H), 3.09 (quin., J =6.8 Hz, 1 H), 2.50–2.06 ppm (m, 6 H); 13 C NMR (100 MHz, CDCl 3 ): δ =216.65, 174.79, 52.22, 41.22, 40.83, 37.50, 26.63 ppm; [ α ]${{{20\hfill \atop {\rm D}\hfill}}}$ =+37.0 ( c =3.5 in CHCl 3 ); Chiral GC (CHIRALDEX G‐TA, injector T =220 °C, detector T =250 °C, column T =100 °C (isothermic), flow=1.0 mL min −1 , t minor =14.7, t major =15.3 min, 95 % ee ; HRMS m / z : calcd for C 7 H 10 O 3 : 142.06299 [ M ] + ; found 142.06301.…”

Nitrilases Catalyze Key Step to Conformationally Constrained GABA Analogous γ-Amino Acids in High Optical Purity

“…The cis enantiomers were also prepared by resolution of their (−)-1-phenylethylammonium salts , In addition to these long-established methods, approaches to cis -3-ACPA comprise multiple-step chirospecific syntheses starting from aspartic acid, asymmetric allylic alkylation of 4-azido-1-benzoyloxycyclopent-2-ene, and the asymmetric reductive amination of (±)-3-oxocyclopentanecarboxylic esters . In fact, few methods took advantage of the benefits of biocatalysis.…”