First Stereoselective Total Synthesis of Ophiocerins B and C

Abstract

An elegant synthesis of ophiocerins B and C is accomplished for the first time with 3R,4R,6R and 3S,4S,6R-configuration. Of these three stereogenic centers, the C-3/C-4 vic-diol was created by Sharpless asymmetric dihydroxylation, while the C-6 stereocenter was achieved from known chiral epoxide. The synthesis of ophiocerins B and C defined the absolute stereochemistry of these natural products.

Key words

Sharpless asymmetric dihydroxylation - ophiocerin - tetrahydropyran derivative

References and Notes

• 1 Reategui RF. Gloer JB. Campbell J. Shearer CA. J. Nat. Prod.  2005,  68:  701 ; and references cited therein
• 2 Oh H. Gloer JB. Shearer CA. J. Nat. Prod.  1999,  62:  497 
• 3a De Albuquerque IL. Galeffi C. Casinovi CG. Marini-Bettolo GB. Gazz. Chim. Ital.  1964,  287 
• 3b Galeffi C. Casinovi CG. Marini-Bettolo GB. Gazz. Chim. Ital.  1965,  95 
• 3c Aragao Craveiro A. da Costa Prado A. Gottlieb OR. Welerson de Albuquerque PC. Phytochemistry  1970,  9:  1869 
• 3d Alcântara AFde C. Souza MR. Pilo-Veloso D. Fitoterapia  2000,  71:  613 
• 4 Nicolau KC. Sorensen EJ. Classics in Total Synthesis   VCH; Weinheim: 1996. 
• 5a Ichimoto I. Tatsumi C. Agric. Biol. Chem.  1964,  28:  723 
• 5b Rosenthal A. Abson D. Can. J. Chem.  1965,  43:  1318 
• 5c Minami T. Moriyama A. Hanaoka M. Synlett  1995,  663 
• 5d Carpintero M. Bastida A. Garcia-Junceda E. Jimenez-Barbero J. Fernandez-Mayoralas A. Eur. J. Org. Chem.  2001,  4127 
• 5e König WA. Lutz S. Mischnick-Luebbecke P. Brassat B. Wenz G. J. Chromatogr.  1988,  447:  193 
• 5f Garegg PJ. Lindberg B. Konradsson P. Kvarnstrom I. Carbohydr. Res.  1988,  176:  145 
• 6 Yadav JS. Bandyopadhyay A. Kunwar AC. Tetrahedron Lett.  2001,  42:  4907 
• 7 Liu HJ. Yip J. Tetrahedron Lett.  1997,  38:  2253 
• 8 Song F. Fidanze S. Benowitz AB. Kishi Y. Org. Lett.  2002,  4:  647 
• 9a Chattopadhyay A. Salaskar A. J. Chem. Soc., Perkin Trans. 1  2002,  785 
• 9b Salaskar A. Sharma A. Chattopadhyay S. Tetrahedron: Asymmetry  2006,  17:  325 

10

Spectroscopic Data for Target Molecules
Ophiocerin B (2): pale yellow oil; [α]_D ²⁵ -34.0 (c 0.25, CH₂Cl₂). IR (neat): ν_max = 3388, 1452, 1380, 1266, 1079, 1004 cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 3.99 (br s, 1 H), 3.97 (dd, 1 H, J = 1.6, 12.4 Hz), 3.85 (ddq, 1 H, J = 2.6, 6.3, 12.0 Hz), 3.73 (dd, 1 H, J = 2.3, 12.2 Hz), 3.47 (br s, 1 H,), 2.21 (d, 1 H, J = 8.0 Hz), 1.81 (ddd, 1 H, J = 3.1, 11.3, 14.3 Hz), 1.64-1.59 (m, 2 H) 1.18 (d, 3 H, J = 6.0 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 68.4, 68.2, 67.4, 67.2, 36.0, 21.1. ESI-MS: m/z = 155 [M + Na]⁺. HRMS: m/z calcd for C₆H₁₂O₃Na: 155.0684 [M⁺ + Na]; found: 155.0691.
Ophiocerin C (3): white solid, mp 80-82 °C; [α]_D ²⁵ +42.2 (c 0.1, CH₂Cl₂). IR (neat): ν_max = 3413, 1460, 1380, 1262, 1136, 1080, 1006 cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 3.98 (dd, 1 H, J = 5.3, 11.4 Hz), 3.61-3.47 (m, 3 H), 3.16 (dd, 1 H, J = 9.8, 11.3 Hz), 2.10-2.05 (br s, 1 H), 2.02-1.97 (m, 2 H), 1.37 (ddd, 1 H, J = 11.3, 11.3, 12.8 Hz), 1.20 (d, 3 H, J = 6.4 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 73.4, 72.6, 72.4, 69.6, 40.5, 21.2. ESI-MS: m/z = 155 [M + Na]⁺. HRMS: m/z calcd for C₆H₁₂O₃Na: 155.0684 [M⁺ + Na]; found: 155.0691.