Concise Diverted Total Synthesis
of Amphidinolide T1 and T4 from a (12E)-Cycloalkene
by Selective Functionalization of the C12-C13 Double Bond

Lijie Sun; Dongdong Wu; Jinlong Wu; Wei-Min Dai

doi:10.1055/s-0031-1289903

LETTER

Concise Diverted Total Synthesis of Amphidinolide T1 and T4 from a (12E)-Cycloalkene by Selective Functionalization of the C12-C13 Double Bond

Lijie Sun^a, Dongdong Wu^b, Jinlong Wu^b, Wei-Min Dai*^a,b
^a Center for Cancer Research and Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, P. R. of China
Fax: +85223581594; e-Mail: chdai@ust.hk;
^b Laboratory of Asymmetric Catalysis and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China
Fax: +86(571)87953128; e-Mail: chdai@zju.edu.cn;

Abstract

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Abstract

Starting from a 19-membered (12E)-cycloalkene prepared by ring-closing metathesis, amphidinolide T1 and T4 were efficiently synthesized via a short sequence of selective functionalization. The key steps highlighted stereoselective dihydroxylation of the (E)-C12-C13 double bond and highly regioselective silylation/desilylation of the (12S,13S)-diol. In particular, a significant solvent effect was discovered for suppressing 1,4 O→O silyl migration or disilylation during selective mono-silylation of the (12R,13R)- and (12S,13S)-diols in toluene. In combination with our previous synthesis of amphidinolide T3, the same (12E)-cycloalkene serves as an advanced common intermediate for concise diverted total synthesis of amphidinolide T family of marine macrolides.

Key words

alkenes - dihydroxylation - macrocycles - osmium - total synthesis

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References

References and Notes

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Chem3D models show that the (13R)-OH group in 5 orients opposite to both the (12R)-OH and the (14R)-Me groups while (13S)-OH group in 6 aligns closely with both the (12S)-OH and the (14R)-Me groups. It should be possible for hydrogen bonding or 1,4 O→O silyl migration to take place in 6 but not in 5.

Characterization Data for Amphidinolide T4 (3): colorless oil; [α]_D ^²0 -9.6 (c = 0.12, CHCl₃), lit.^4b,4d,7a [α]_D ^²³
-7.5 (c = 0.8, CHCl₃), [α]_D ^²0 -3.0 (c = 0.12, CHCl₃); R _f 0.35 (20% EtOAc in hexane). IR (film): 3458 (br), 2934, 1724, 1459, 1252, 1071 cm^-¹. ^¹H NMR and ^¹³C NMR data are identical to those of natural amphidinolide T4 (see Figures S3 and S4 in the Supporting Information). HRMS (+ESI): m/z [M + H⁺] calcd for C₂₅H₄₃O₅: 423.3111; found: 423.3116.

Characterization Data for Amphidinolide T1 (1): colorless oil; [α]_D ^²0 +20.3 (c = 0.15, CHCl₃), lit.^³a [α]_D ^²0 +18 (c = 0.3, CHCl₃); R_f 0.27 (17% EtOAc in hexane). IR (film): 3401 (br), 2928, 1727, 1463, 1253, 1060 cm^-¹; ^¹H NMR and ^¹³C NMR data are identical to those of natural amphidinolide T1 (see Figures S1 and S2 in the Supporting Information). HRMS (+ESI): m/z [M + H⁺] calcd for C₂₅H₄₃O₅: 423.3111; found: 423.3104.

Supplementary Material

Supporting Information