Asymmetric Synthesis of Nabscessin A from Inositol and d-Camphor

Abstract

An enantiomer of nabscessin A (1), an aminocyclitol amide with antimicrobial activity, was synthesized from myo-inositol and dimethyl d-camphor acetal in 14 steps. Formal synthesis of natural nabscessin A was also achieved through the new approach to access both enantiomers of 4,5-di-O-benzyl-myo-inositol, derived from the same set of starting materials. This synthesis features utilizations of the existing framework of myo-inositol and a regioselective esterification.

Enantioselective Synthesis of Nabscessin C

“…Mp 139.0−140.0 °C; 1 H NMR (300 MHz, CDCl 3 ) δ 7.37−7.27 (m, 10H), 4.92 (d, J = 11.5 Hz, 2H), 4.78 (d, J = 11.5 Hz, 2H), 3.60−3.50 (m, 3H), 3.24 (t, J = 9.2 Hz, 2H), 2.51 (s, 1H), 2.30 (s, 2H), 2.22−2.14 (m, 1H), 1.48 (dd, J = 24.3, 12.0 Hz, 1H); 13 C{ 1 H} NMR (75 MHz, CDCl 3 ) δ 138. 5, 128.7, 128.1, 128.0, 86.0, 75.1, 74.9, 68.7, 36. meso-(1S,2R,3R,5S,6S)-2,6-Bis(benzyloxy)-3,5-bis((triethylsilyl)oxy)cyclohexan-1-ol (8). Triethylchlorosilane (28.9 mg, 32.1 μL, 0.19 mmol) was added to a solution of 7 (30.0 mg, 0.09 mmol) and pyridine (0.5 mL) at 0 °C.…”

“…O- (8,9-Bis(benzyloxy)-2,4,10-trioxaadamantan-6-yl) S-Methyl Carbonodithioate (5). Sodium hydride (NaH 60% in mineral oil,10.8 mg, 0.27 mmol) was added to a solution of 4 (50.0 mg, 0.13 mmol) in THF (4.3 mL) at 0 °C.…”

“…The first synthesis of nabscessin B was reported by Banwell’s group, in which they constructed the carbocycle by ring-closing metathesis starting from l -tartaric acid (Scheme ). Furthermore, recently we reported the asymmetric synthesis of nabscessin A through the desymmetrization of meso myo -inositol with d -camphor . In contrast to Banwell’s synthesis to construct the cyclitol framework from scratch, our approach utilizes the inherent cyclohexane scaffold and the established protocols/selectivities in manipulating myo -inositol to prepare DOIA-related compounds. , In the current article, our progress in the synthesis of nabscessin C ( 1 ), also starting from myo -inositol, is reported.…”

“…Although nabscessins A–C are isomers which differ only in the linkage of the 2-hydroxy-6-methylbenzoyl group to aminocyclitol, the methods previously used to synthesize nabscessins A and B are not suitable for nabscessin C synthesis. , This is because the C3-hydroxyl group, which is the site for linking the ester group in nabscessin C, is protected with the neighboring C2- or C4-hydroxyl group as a diacetal in both methods (Scheme ). If either of these methods is used to synthesize nabscessin C ( 1 ), the challenging regioselective esterification at the C3-hydroxyl becomes difficult to circumvent after the removal of diacetal.…”

Access to Enantiomeric Organic Compounds with Potential for Synthesis via Racemic Conglomerates: Inositol Derivatives as a Case in Point

“…Synthesis of enantiomerically pure organic compounds and resolution of racemates have gained unprecedented significance due to different properties of enantiomers and racemates, e.g ., the therapeutic efficacy of drugs. − Enantiomeric organic compounds can be extracted routinely from natural sources, although with wide variation in inputs in terms of cost, effort, and time. Due to the high enantiomeric purity of organic compounds isolable from natural sources, many of them form the starting materials for the synthesis of natural and unnatural chiral molecular entities. − Most laboratory methods of preparation of enantiomeric compounds involve the use of enantiomeric molecular entities such as catalysts (including enzymes) for asymmetric synthesis, chiral auxiliaries, resolving agents, or chiral stationary phases for the separation of enantiomers (in a racemate). ,− Almost all of these methods to obtain enantiomers depend on the solution-state chemistry. Enantiomers present in a racemate can also be separated by preferential enrichment of enantiomers and by preferential crystallization of conglomerates .…”