Synlett 2019; 30(06): 709-712
DOI: 10.1055/s-0037-1610694
letter
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of PF1163B

Aakash Sengupta
,
Department of Applied Chemistry, Faculty of Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555, Japan   Email: seijiro@waseda.jp
› Author Affiliations
We are grateful for the financial support from the Sumitomo Foundation and the Tokyo Biochemical Research Foundation. This work was also supported by Grant-in-Aid for Scientific Research on Innovative Areas ‘Frontier Research on Chemical Communications’ (Grant no. 18H04632).
Further Information

Publication History

Received: 27 December 2018

Accepted after revision: 23 January 2019

Publication Date:
20 February 2019 (online)


Abstract

A total synthesis of PF1163B has been achieved. The vinylogous Mukaiyama aldol reaction of ketene silyl N,O-acetal 6 (ent-6) mediated by excess TiCl4 proceeded with saturated aldehydes to give adduct 10 in moderate yield with moderate stereoselectivity. The major isomer is the diastereomer that was provided by using one equivalent of TiCl4. The Birch reduction of α,β-unsaturated imide 4, possessing a less hindered side chain, gave 12 in good stereoselectivity by employing 2-isopropylbenzimidazole as a bulky proton source. After elongation of the carbon chain and connection with the amino acid part, we accomplished a total synthesis of PF1163B. These methods constitute a concise synthetic route to obtain polyketides as well as depsipeptides.

Supporting Information

 
  • References and Notes

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  • 10 Synthesis of PF1163B (1) from Acyclic 17 To a solution of compound 17 (85.9 mg, 0.114 mmol) in CH2Cl2 (4.0 mL) at 0 °C was added TFA (1.0 mL, 98%). The reaction mixture was stirred for 35 min at rt and then concentrated. The residue was then taken up in CH2Cl2 (64.0 mL) and cooled to 0 °C. Et3N (0.19 mL, 1.368 mmol) was added dropwise, followed by the addition of BOP-Cl (174.1 mg, 0.684 mmol). The reaction mixture was stirred at 0 °C for 48 h. Then, it was concentrated and NaHCO3 aq. (2.0 mL) was added. The aqueous layer was extracted two times with CHCl3 (4.0 mL × 2) and the combined organic layers were concentrated, dried with Na2SO4, and purified by silica gel chromatography (n-hexane/EtOAc = 5:1) to give PF1163B (1) (27.0 mg, 0.058 mmoles, 50% over 2 steps) as a colorless oil. Rf = 0.48 (n-hexane/EtOAc = 1:1). [α]D 23 = –109.6 (c 0.49, MeOH). 1H NMR (400 MHz, CDCl3): δ = 7.21–7.05 (2 H, m), 6.88–6.79 (2 H, m), 5.84–5.75 (0.6 H, m), 4.94–4.78 (1 H, m), 4.60–4.54 (0.27 H, m), 4.09–4.01 (2 H, m), 3.99–3.91 (2 H, m), 3.60–3.14 (4 H, m), 3.04–2.90 (3 H, m), 2.84–2.61 (2 H, m), 2.47–1.96 (4 H, m), 1.54–1.03 (16 H, m), 0.92–0.79 (6 H, m). 13C NMR (100 MHz, CDCl3): δ = 173.4, 171.1, 170.2, 157.2, 130.2, 129.7, 129.1, 114.9, 114.4, 75.3, 69.1, 69.0, 61.5, 55.4, 35.1, 35.0, 34.0, 33.7, 33.6, 33.5, 31.7, 31.6, 29.4, 29.3, 28.7, 26.5, 25.0, 20.5, 14.0. HRMS-ESI: m/z [M + Na]+ calcd for C27H43O5NNa: 484.3033; found: 484.3033. IR (KBr): 3400, 2950, 2929, 1731, 1632, 1512, 1248, 1220, 1078, 772 cm–1.