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. Author manuscript; available in PMC: 2013 Aug 11.
Published in final edited form as: Angew Chem Int Ed Engl. 2010 Aug 16;49(35):6151–6155. doi: 10.1002/anie.201002293

Scheme 3.

Scheme 3

Synthesis of fragment 3 via the relay ring-closing metathesis reactions of substrates 5a and 5b. Reagents and conditions: (a) i) 15, Ph2SiCl2, pyridine, RT; ii) 14, pyridine, 41%; (b) G2, PhCH3, N2, 65 °C, 92%; (c) i) TBAF, THF, RT, 93%; ii) TBSCl, Et3N, DMF, RT, 84%; iii) Cl3CC(=NH)OPMB, CSA, DCM, RT, 76%; (d) i) RhCl3·3H2O, EtOH/H2O, 80 °C, 98% (15:1 = E:Z); ii) LiOH, H2O2, THF/H2O, 0 °C, 99%; (e) 15, DCC, DMAP, DCM, 0 °C to RT, 82%; (f) G2, DCM, 45 °C, 70%; (g) i) NaBH4, AcOH, EtOH, 0 °C to RT, 82%; ii) TBSCl, Et3N, DMAP, DCM, RT, 99%; iii) Cl3CC(=NH)OPMB, CSA, DCM, RT, 77%; (h) i) Zn°, Cp2TiCl2, allyl 2-bromoacetate, THF, 60 °C; ii) pH 3 buffer, i-PrOH/H2O/THF, RT; (i) Pd(PPh3)4, HCO2H, Et3N, THF, RT, 61% (over 3 steps). (j) CH2=CH2 (15 psi), G2, PhH, 65 °C, quantitative. G2 = second generation Grubbs initiator, [Ru=CHPh(Cl)2(PCy3)(H2IMes)]; [Ru*] = Ru(Cl)2(H2IMes)Ln; TBAF = tetrabutylammonium fluoride; DCC = dicyclohexylcarbodiimide.