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. 2011 Jun 20;50(26):5892-5.
doi: 10.1002/anie.201102037. Epub 2011 May 10.

Synthesis of (-)-okilactomycin by a Prins-type fragment-assembly strategy

Jason M Tenenbaum  1 , William J Morris, Daniel W Custar, Karl A Scheidt
Affiliations

Synthesis of (-)-okilactomycin by a Prins-type fragment-assembly strategy

Jason M Tenenbaum et al. Angew Chem Int Ed Engl. .
No abstract available

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Figures

Scheme 1
Scheme 1
Retrosynthetic strategy. TBDPS =tert-butyldiphenylsilyl.
Scheme 2
Scheme 2
Synthesis of cyclohexene 3. Reagents and conditions: a) Cp2Zr(H)Cl, NIS, THF, 84 % b) nBuLi, THF, −78 °C; then 7, 23°C, 65%. c) KHMDS, ethyltriphenylphosphonium bromide, THF, −78 to 0°C, 84%. d) Et2AlCl, AgPF6, CH2Cl2, −78 °C, 86 %, >20:1 d.r. 1e) LiBH4, MeOH, Et2O, 0 °C, 83%. f) Dess–Martin periodinane, CH2Cl2, 90%. g) TBSOTf, NEt3, CH2Cl2. h) DMDO, CH2Cl2, 0 °C; then acidic work-up, 88% over two steps. Bn =benzyl, Cp =cyclopenta-dienyl, DMDO=dimethyldioxirane, HMSD=hexamethyldisilazide, NIS =N-iodosuccinimide, TBS =tert-butyldimethylsilyl, THF =tetrahy-drofuran.
Scheme 3
Scheme 3
Synthesis of intermediates 4 and 17. Reagents and conditions: a) Cu(OTf)2, (R)-tol-binap, TBAT, THF, −50 °C, 70 %, 10:1 d.r. b) TBSOTf, 2,6-lutidine, CH2Cl2, 0 °C, 92%. c) NH4F, MeOH, 40 °C, 92%. d) 1. o-nitrophenyl selenocyanate, PBu3, THF; 2. H2O2, THF, 76%. e) HF·py, THF, 93 %. f) KOEt, CH2Cl2, 88%. g) HF·py, THF 94%. py =pyridine, TBAT =tetrabutylammonium difluorotriphenylsilicate, tol-binap=2,2′-Bis(di-p-tolylphosphino)-1,1′-binaphthyl. OTf =trifluoro-methanesulfononate.
Scheme 4
Scheme 4
Proposed pathway for the formation of 18. M.S. =molecular sieves.
Scheme 5
Scheme 5
Completion of the synthesis of (−)-okilactomycin. Reagents and conditions: a) aq HF, CH3CN. b) KOtBu, CH2Cl2. c) K2CO3, MeI, CH3CN, 70 °C, 58% over three steps). d) TBDPSCl, imidazole, CH2Cl2, 90%. e) DDQ (30 equiv), CH2Cl2, 61%. f) 1. o-nitrophenyl-selenocyanate, PBu3, THF; 2. H2O2, THF, 60%. g) Grubbs second-generation catalyst (40 mol%), CH2Cl2, 40 °C. h) H2, PtO2, EtOAc, 65 % over two steps. i) HF·py, THF, >99% j) LiHMDS, dimethylmethylideneammonium iodide, THF 95%. k) Dess–Martin periodinane, CH2Cl2, 83% l) NaClO2, NaH2PO4, 2-methyl-2-butene, tBuOH/THF/H2O (4:4:1), 50%. DDQ =2,3-dichloro-5,6-dicyanobenzoquinone.
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References

    1. Imai HS, Kaniwa H, Tokunaga T, Fujita S, Furuya T, Matsumoto H, Shimizu M. J Antibiot. 1987;40:1483–1489. - PubMed
    2. Imai HS, Suzuki KI, Morioka M, Numasaki Y, Kadota S, Nagai K, Sato T, Iwanami M, Saito T. J Antibiot. 1987;40:1475–1482. - PubMed
    3. Nakai R, Kakita S, Asai A, Chiba S, Akinaga S, Mizukami T, Yamashita Y. J Antibiot. 2001;54:836–838. - PubMed
    4. Nakai R, Ishida H, Asai A, Ogawa H, Yamamoto Y, Kawasaki H, Akinaga S, Mizukami T, Yamashita Y. Chem Biol. 2006;13:183–189. - PubMed
    1. Takeda K, Shimotani A, Yoshii E, Yamaguchi K. Heterocycles. 1992;34:2259–2261.
    2. Boulet SL, Paquette LA. Synthesis. 2002:895–900.
    3. Paquette LA, Boulet SL. Synthesis. 2002:888–894.
    4. Smith AB, III, Basu K, Bosanac T. J Am Chem Soc. 2007;129:14872–14874. - PubMed
    5. Smith AB, III, Bosanac T, Basu K. J Am Chem Soc. 2009;131:2348–2358. - PMC - PubMed
    1. Cloninger MJ, Overman LE. J Am Chem Soc. 1999;121:1092–1093.
    2. Zhang WC, Viswanathan GS, Li CJ. Chem Commun. 1999:291–292.
    3. Crosby SR, Harding JR, King CD, Parker GD, Willis CL. Org Lett. 2002;4:3407–3410. - PubMed
    4. Jasti R, Vitale J, Rychnovsky SD. J Am Chem Soc. 2004;126:9904–9905. - PubMed
    5. Chan KP, Loh TP. Org Lett. 2005;7:4491–4494. - PubMed
    6. Chan KP, Ling YH, Loh TP. Chem Commun. 2007:939–941. - PubMed
    7. Liu F, Loh T-P. Org Lett. 2007;9:2063–2066. - PubMed
    8. Pastor IM, Yus M. Curr Org Chem. 2007;11:925–957.
    9. Van Orden LJ, Patterson BD, Rychnovsky SD. J Org Chem. 2007;72:5784–5793. - PMC - PubMed
    10. Bahnck KB, Rychnovsky SD. J Am Chem Soc. 2008;130:13177–13181. - PMC - PubMed
    11. Elsworth JD, Willis CL. Chem Commun. 2008:1587–1589. - PubMed
    1. Hart DW, Schwartz J. J Am Chem Soc. 1974;96:8115–8116.
    2. Schwartz J, Labinger JA. Angew Chem. 1976;88:402–409.
    3. Angew Chem Int Ed Engl. 1976;15:333–340.
    1. Maryanoff BE, Reitz AB. Chem Rev. 1989;89:863–927.

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