@article{6085b57a395e44dc9ffae671fc701104,
title = "Synthesis and structure revision of the myo-inositol monophosphatase inhibitor l-671,776",
abstract = "Concomitant deprotection/spiro-heteroannulation of 6 utilizing (EtO)3SiI was exploited for the asymmetric total synthesis of the title tetracyclic terpenoid whose structure was revised to 13.",
author = "Falck, {J. R.} and {Kishta Reddy}, K. and S. Chandrasekhar",
note = "Funding Information: Acknowledgment: Supported financially by the Robert A. Welch Foundation and the USPHS NIH (GM31278). Dr. Y.K. Tony Lam (Merck & Co) is thanked for helpful discussions and a sample of natural L-671,776. References and Notes 1. Piettre, S.R.; Ganzhorn, A.; Hoflack, J.; Islam, K.; Homsperger, J.-M. J. Am. Chem. Soc. 1997, 119, 3201-3204 and cited references. 2. Barchas, J.D.; Hamblin, M.W.; Malenka, R.C. Biochemical Hypotheses of Mood and Anxiety Disorders. In Basic Neurochemistry: Molecular, Cellular, and Medical Aspects 5th ed.; Siegel, G.J., et al., eds.; Raven Press: New York, 1994, pp.979-1002. 3. Lam, Y.K.T.; Wichmann, C.F.; Meinz, M.S.; Guariglia, L.; Giacobbe, R.A.; Mochales, S., Kong, L.; Honeycutt, S.S.; Zink, D.; Bills, G.F.; Huang, L.; Burg, R.W.; Monaghan, R.L.; Jackson, R.; Reid, G.; Maguire, J.J.; McKnight, .T.; Ragan, C.I.J. Antibiot. 1992, 45, 1397-1403. 4. Falck, J.R.; Reddy, K.K.; Chandrasekhar, S. ACS 206th National Meeting, Chicago, II, Aug. 22-27, 1993; Div. Med. Chem. Abst. 222. 5. A similar conclusion was reached independently based on extensive NMR analysis: Ferrari, P.; Stefanelli, S.; Islam, K. J. Chem. Res. (S) 1995, 110-111. 6. The structurally related K-76 also displays non-competitive inhibition of inositol monophosphatase: Pachter, J.A. Molecular Pharmacology 1991, 40, 107-111. 7. The same and several closely related, bioactive metabolites have been isolated: Kaneto, R.; Dobashi, K.; Kojima, I.; Sakai, K.; Shibamoto, N.; Okamoto, R.; Akagawa, H.; Mizuno, S. J. Antibiot. 1994, 47, 727-730. Stefanelli, S.; Sponga, F.; Ferrari, P.; Sottani, C.; Corti, E.; Brunati, C.; Islam, K. ibid. 1996, 49, 611-615. Chu, M.; Mierzwa, R.; Truumees, I.; King, A.; Patel, M.; Pichardo, J.; Hart, A.; Dasmahapatra, B.; Das, P.R4 Puar, M.S. Tetrahedron Lett. 1996, 37, 3943-3946. Ayer, W.A.; Miao, S. Can. J. Chem. 1993, 71,487-493. 8. Falck, J.R.; Manna, S.; Chandrasekhar, S.; Alcaraz, L.; Mioskowski, C. Tetrahedron Lett. 1994, 35, 2013-2016. 9. Earnshaw, C.; Wallis, C.J.; Warren, S. J.C.S. Perkin Transactions 1 1979, 3099-3106. 10. Compare with related spiro-heteroannulations: Morrison, G.A.; Sammes, P.G.; Simmonds, J.P. Heterocycles 1989, 28, 1037-1050. Corey, E.J.; Das, J. J. Am. Chem. Soc. 1982, 104, 5551-5553. 11. The stereochemistry of 7 was assigned using extensive 1H NMR analysis with analogy to the structurally similar examples described in ref. 10. 12. In addition to ether cleavage, recent evaluations of (EtO)3SiI show it is a milder and more selective reagent than Me3SiI for other types of reactions. Details will be reported elsewhere. 13. Wynberg, H.; Meijer, E.W. Org. React. 1982, 28, 2. 14. Kajigaeshi, S.; Kakinami, T.; Okamoto, T.; Nakamura, H.; Fuijawa, M. Bull. Chem. Soc. Jap. 1987, 60, 4187-4189. 15. Spectral data ior 8: 1HNMR(250MHz, CDCI3)~0.70(d,J=6.4Hz, 3H), 0.94(s, 3 H), 0.96 (s, 3H), 1.04 (s, 12 H), 1.12 (s, 9 H), 1.26-1.84 (m, 10 H), 2.75 (d, J = 16.4 Hz, 1 H), 3.10 (d, J = 16.4 Hz, i H), 3.38 (dd, J = 4.3, 11.5 Hz, 1 H), 4.62 (s, 2 H), 5.50 (s, 1 H, D20 exchangeable), 6.65 (s, 1 H), 7.30-7.49 (m, 12 H), 7.63-7.72 (m, 8 H). 11: IH NMR (250 MHz, CDCI3) 8 0.67 (d, J = 6.4 Hz, 3 H), 0.92 (s, 3 H), 0.94 (s, 3 H), 0.96 (s, 3 H), 1.04 (s, 9 H), 1.09 (s, 9 H), 1.19-1.69 (m, 10 H), 2.79 (d, J = 16.1 Hz, 1 H), 3.11 (d, J = 16.1 Hz, 1 H), 3.32 (dd, J = 4.1, 11.4 Hz, 1 H), 4.68 (s, 2 H), 5.12 (s, 1 H, D20",
year = "1997",
month = jul,
day = "28",
doi = "10.1016/S0040-4039(97)01146-5",
language = "English (US)",
volume = "38",
pages = "5245--5248",
journal = "Tetrahedron Letters",
issn = "0040-4039",
publisher = "Elsevier Limited",
number = "30",
}