Asymmetric Total Synthesis of (+)‐Neooxazolomycin Using a Chirality‐Transfer Strategy

Abstract

The total synthesis of (+ +)-neooxazolomycin was achieved from the amino-acid d-serine.T he efficiency of this approach is derived from the use of principles of memory of chirality and dynamic kinetic resolution in the intramolecular aldol reaction of as erine derivative to build the densely functionalizedl actam framework and to install three contiguous stereocenters.T he key intermediate was readily elaborated to the target natural product.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Acyclic Twisted Amides

“… ,− As expected, comparatively fewer examples of structurally characterized N-pyramidalized amides embedded in six-membered rings have been reported; however, these amides feature significant N-pyramidalization (average χ N of 46.1°), while twist is much lower (average τ of 11.2°). These values compare well with the five-membered fused ring lactams (χ N , 45.9°; τ, 11.7°), − ,− …”

“…Similar to β-lactams, the amide bond geometry of structurally characterized amides embedded in a fused five-membered ring system (Figures –) − ,− can be characterized as N-pyramidalized (average χ N of 45.9°) with minimal twist (average τ of 11.7°). As expected, the average values of N-pyramidalization and twist are slightly lower as compared to β-lactams ...…”

“…Most common in this class (Figures –) − ,− is ring fusion to six-membered rings in a [ 3 .4.0] scaffold, including piperazine, such as 4.120 , and hexahydropyrimidine, such as 4.121 , and much more common [ 3 .3.0] ring system with the ring fusion to five-membered rings, including pyrrolidine, such as 4.122 , thiazolidine, such as 4.123 ,…”

“…This class also includes benzo-fused lactams, such as 4.140 , 4.146 , and 4.173 , and tricyclic fused ring systems, such as 4.138 , 4.171 , 4.172 , and 4.181 . In general, increased substitution at the α-position to the nitrogen atom and additional constraints of the five-membered ring, such as unsaturation, conformationally rigid ring systems, and steric effects, lead to higher N-pyramidalization. − ,− …”

Oxazolomycins produced by Streptomyces glaucus and their cytotoxic activity

“…[16][17][18] The unique structure and multiple biological activities of oxazolomycins has attracted much attention from organic chemists. The total synthesis of neooxazolomycin, 19,20 oxazolomycin A, 21 and lajollamycin 22 has been accomplished. In addition, several synthesis method to establish the different structural segments of oxazolomycins have been reported.…”