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. 2010 Jul 21;132(28):9567-9.
doi: 10.1021/ja1035495.

Total synthesis of (+/-)-aplykurodinone-1: traceless stereochemical guidance

Yandong Zhang  1 , Samuel J Danishefsky
Affiliations

Total synthesis of (+/-)-aplykurodinone-1: traceless stereochemical guidance

Yandong Zhang et al. J Am Chem Soc. .

Erratum in

  • J Am Chem Soc.2010 Jul 21;132(28):9928

Abstract

The total synthesis of the highly degraded steroidal natural product, aplykurodinone-1 (1), has been accomplished. Key features include a one-flask hydrolysis/retro-aldol/iodolactonization sequence to excise the C(8) hydroxymethylene functionality with retention of stereochemistry and the stereoselective installation of the C(13) methyl group through hydrogenation with homogeneous catalyst.

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Figures

Scheme 1
Scheme 1
Synthetic Strategy Toward Aplykurodinone-1 (1).
Scheme 2
Scheme 2
Synthesis of 6 En Route to Aplykurodinone-1 (1). aKey: (a) MeLi, DME/THF, −50 °C; TFA, CHCl3, reflux, 73%; (b) HSCH2CH2SH, AcOH, p-TSA, 74%; (c) NaBH4, CH2Cl2/MeOH, −78 °C→ −40 °C; (d) MOMCl, iPr2NEt, CH2Cl2, 84% over 2 steps; (e) DIBAL-H, CH2Cl2, −78 °C; (f) Tl(NO3)3, MeOH/THF/H2O, 95% over 2 steps; (g) TsNHN=CHCOCl, PhNMe2, Et3N, CH2Cl2, 0 °C, 88%; (h) bis-(N-t-butylsalicylaldiminato) copper (II), PhMe, reflux, 40%; (i) NaBH4, CeCl3•7H2O; (j) I2, PPh3, imidazole, PhMe, reflux, 78% over 2 steps; (k) SmI2, THF/MeOH, 85%; (l) HCl, THF/H2O; (m) DMP, CH2Cl2, 80% over 2 steps.
Scheme 3
Scheme 3
aKey: (a) K2CO3, H2O, 100 °C; (b) NIS, CH2Cl2, 75%; (c) Ra-Ni, CH2Cl2/EtOH, 90%; (d) TMSOTf, Et3N, CH2Cl2, 0 °C; Pd(OAc)2, CH3CN, 76% (90% brsm).
Scheme 4
Scheme 4
aKey: (a) 17, t-BuLi, CuCN, BF3•OEt2, −78 °C→ −98 °C, 73%, 10:1 dr; (b) Crabtree catalyst, H2, CH2Cl2, 75% conversion, 50% yield (pure); (c) HF, CH3CN/THF; (d) DMP, CH2Cl2, 87% over two steps; (e) THF, LiHMDS, −78 °C, 68%.
Scheme 5
Scheme 5
aKey: (a) 17, t-BuLi, CuCN, Et2O, −78 °C, 51%; (b) Wilkinson catalyst, H2, benzene, 67%.
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