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Synlett 2020; 31(16): 1623-1628
DOI: 10.1055/s-0040-1707198
letter
© Georg Thieme Verlag Stuttgart · New York

Synthetic Study on Lactonamycins, Part 2: Stereoselective Access to ABCD-Ring System

Hiroshi Takikawa 
,
Kazuki Murata
,
Shogo Sato
,
Takuma Kawada
,
Hiroshi Nakakohara
,
Ken Ohmori 
,
Keisuke Suzuki  ∗
Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8551, Japan   Email: ksuzuki@chem.titech.ac.jp
› Author AffiliationsThis work was supported by Grants-in-Aid from the Japan Society for the Promotion of Science (JSPS) (Nos. JP16H06351 and JP18K06548).
Further Information

Publication History

Received: 28 May 2020

Accepted after revision: 18 June 2020

Publication Date:
21 July 2020 (online)

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Dedicated to the memory of Prof. Hidetoshi Yamada

Abstract

Toward a stereoselective total synthesis of the lactonamycins, we recently reported an approach to the DEF-ring system. Here we report a model study for constructing the ABCD-ring system, revealing a viable approach through (1) construction of the C-ring by asymmetric benzoin cyclization, (2) introduction of an angular hydroxy group through oxidation of an isoxazolium salt, and (3) construction of the AB rings through a ring-opening/closing sequence.

Key words

natural products - total synthesis - lactonamycins - aromatic polyketides - isoxazoles - benzoin cyclization

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707198.
  • Supporting Information
 

  • References and Notes

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  • 29 The Z geometry of 20 was tentatively assigned by considering the steric disadvantage of the corresponding β-elimination of K → (E)-20 (Figure 4).
  • 30 The corresponding sulfide having a benzoyl protection, rather than a p-nitrobenzoyl group, was subjected to the same sequence of reactions, giving the lower yield of 20 (60%).
  • 31 By omitting the purification operation after the first step, the two-step yield of 23 from 19 was improved to 88%.
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  • 34 1H NMR analysis showed a single geometrical isomer. The configuration of the enol ether moiety was tentatively shown to be Z.
  • 35 Acid-catalyzed conversion of 29 into 28 (CSA, MeOH, CH2Cl2, reflux) was unsuccessful. For related observations, see ref. 5b.