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. 2009 Feb 4;131(4):1410-2.
doi: 10.1021/ja808110d.

Synthesis and structure revision of nakiterpiosin

Shuanhu Gao  1 , Qiaoling Wang, Chuo Chen
Affiliations

Synthesis and structure revision of nakiterpiosin

Shuanhu Gao et al. J Am Chem Soc. .

Abstract

This manuscript describes a convergent synthesis and the revision of the relative stereochemistry of nakiterpiosin, a marine C-nor-D-homosteroid. Our synthesis features a late-stage carbonylative Stille cross-coupling reaction and a photo-Nazarov cyclization reaction that deliver the complete nakiterpiosin skeleton efficiently.

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Figures

Figure 1
Figure 1
The C-nor-D-homosteroids.
Figure 2
Figure 2
Our synthetic approach to 1.
Scheme 1
Scheme 1
The synthesis of 6a aReaction conditions: (a) CDI, NH(OMe)Me•HCl, CH2Cl2, 23 °C, 74%. (b) 2 mol % RuCl[(S,S)-TsDPEN](p-cymeme), HCOONa, H2O, 40 °C, 87%, 91% ee. (c) H2C=C(Me)MgBr, THF, 0 to 23 °C, 84%. (d) Me2AlCl, CH2Cl2, −78 to −30 °C, 71%. (e) DMAP, ArSO2Cl, CH2Cl2, 0 to 23 °C, 100%; Ar = 2-(MeOOC)Ph. (f) 20 mol % OsO4, NMO, acetone, H2O, 23 °C, 89%. (g) LiBr, acetone, 70 °C, 62%. (h) KHMDS, PhNTf2, THF, −78 °C, 96%.
Scheme 2
Scheme 2
Synthesis of 7 and completion of the synthesis of 1a aReaction conditions: (a) 15 mol % Ti(OiPr)4, 18 mol % (−)-diethyl tartrate, tBuOOH, 4Å MS, CH2Cl2, −20 °C, 98%, 92% ee. (b) TBSCl, imidazole, DMF, 23 °C, 97%. (c) (Ar′O)2AlMe, CH2Cl2, −78 °C, 79%, 71% ee; Ar′ = 4-Br-2,6-tBu2-Ph. (d) 10 mol % Bi(OTf)3, 3-Me-2-TIPSO-furan, CH2Cl2, −40 °C, 76% (56% conversion), dr 11:1, 60% ee. (e) H2, 10 mol % [(cod)Ir(PCy3)(Py)]PF6, CH2Cl2, 23 °C, 97%, dr 6:1. (f) Dess-Martin periodinane, H2O, CH2Cl2, 23 °C, 98%. (g) NaBH4, THF, EtOH, −78 °C, 93%. (h) TBSOTf, 2,6-lutidine, CH2Cl2, 40 °C, 93%. (i) 1) HOAc, THF, H2O, 60 °C, 76%. (j) Dess-Martin periodinane, H2O, CH2Cl2, 23 °C, 91%. (k) Cl2, P(OPh)3, NEt3, CH2Cl2, −78 °C, 83%. (l) 45 mol % Pd(PPh3)4, Me3Sn–SnMe3, dioxane, 100 °C, 50%. (m) 1 atm CO, Pd(PPh3)4, CuCl, DMSO, 55 °C, 62%. (n) hν (350 nm), CH3CN, 23 °C. (o) iPr2NH, MeOH, 50 °C, 60% for two steps. (p) TFA, CH2Cl2, H2O, 23 °C. (q) NaIO4, acetone, pH 7.4 buffer, 23 °C. (r) BF3•OEt2, Et3SiH, CH2Cl2, 0 to 23 °C, 44% for three steps. (s) TBAF, THF, 23 °C, 79%.
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References

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