Asymmetric Total Synthesis of Pseudoplexaurol and 14-Deoxycrassin, two Antitumor Marine Cembrane Diterpenoids

Zuosheng Liu; Lizeng Peng; Weidong Z. Li; Yulin Li

doi:10.1055/s-2003-42077

LETTER

Asymmetric Total Synthesis of Pseudoplexaurol and 14-Deoxycrassin, two Antitumor Marine Cembrane Diterpenoids

Zuosheng Liu, Lizeng Peng, Weidong Z. Li, Yulin Li*
National Laboratory of Applied Organic Chemistry and Institute of Organic Chemistry Lanzhou University, Lanzhou, Gansu 730000, P. R. China
Fax: +86(931)8912283; e-Mail: lilyl@lzu.edu.cn;

Abstract

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Abstract

The first asymmetric total synthesis of two naturally occurring antitumor pseudoplexaurol and 14-deoxycrassin were achieved via two convergent synthetic sequences featured a chiral pool protocol to implement C-1 stereogenic center and Ti(0)-mediated cyclization leading to cembrane ring.

Key words

14-deoxycrassin - diterpenoids - cembranoids - total synthesis

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References

<A NAME="RU11303ST-1">1</A> Tursch B. Braeckman JC. Dolaze D. Kaisin M. In Marine Natural Products: Chemical and Biological Perspectives Vol. 2: Scheuer PJ. Academic Press; New York: 1978. p.247-296

<A NAME="RU11303ST-2">2</A> Rodríguez AD. Tetrahedron 1995, 51: 4571

<A NAME="RU11303ST-3A">3a</A> Tius MA. Chem. Rev. 1988, 88: 719

<A NAME="RU11303ST-3B">3b</A> Cox NJG. Mills SD. Pattenden G. J. Chem. Soc., Perkin Trans. 1 1992, 1313 ; and references cited therein

<A NAME="RU11303ST-4">4</A> Rodríguez AD. Martínez N. Experientia 1993, 49: 179

<A NAME="RU11303ST-5">5</A> Rodríguez AD. Acosta AL. J. Nat. Prod. 1997, 60: 1134

<A NAME="RU11303ST-6">6</A> Rodríguez AD. Li YX. Dhasmana H. Barnes CL. J. Nat. Prod. 1993, 56: 1101

<A NAME="RU11303ST-7">7</A> Rodríguez AD. Piña IC. Acosta AL. Ramírez C. Soto JJ. J. Org. Chem. 2001, 66: 648

<A NAME="RU11303ST-8A">8a</A> Tius MA. Reddy NK. Tetrahedron Lett. 1991, 32: 3605

<A NAME="RU11303ST-8B">8b</A> Dauben WG. Wang TZ. Stephens RW. Tetrahedron Lett. 1990, 31: 2393

<A NAME="RU11303ST-8C">8c</A> McMurry JE. Dushin RG. J. Am. Chem. Soc. 1990, 112: 6942

<A NAME="RU11303ST-8D">8d</A> McMurry JE. Dushin RG. J. Am. Chem. Soc. 1989, 111: 8928

<A NAME="RU11303ST-8E">8e</A> Marshall JA. Andrews RC. Lebioda L. J. Org. Chem. 1987, 52: 2378

<A NAME="RU11303ST-8F">8f</A> Dauben WG. Saugier RK. Fleischhauer I. J. Org. Chem. 1985, 50: 3767

<A NAME="RU11303ST-8G">8g</A> Marshall JA. Royce RD. J. Org. Chem. 1982, 47: 693

For reviews, see:

<A NAME="RU11303ST-9A">9a</A> Fürstner A. Bogdanovic B. Angew. Chem., Int. Ed. Engl. 1996, 35: 2442

<A NAME="RU11303ST-9B">9b</A> McMurry JE. Chem. Rev. 1989, 89: 1513

<A NAME="RU11303ST-9C">9c</A> Lenoir D. Synthesis 1989, 883

<A NAME="RU11303ST-9D">9d</A> McMurry JE. Acc. Chem. Res. 1983, 16: 405

For recent synthetic works on epoxy cembranolides from this laboratory, see:

<A NAME="RU11303ST-10A">10a</A> Liu ZS. Li WDZ. Li YL. Tetrahedron: Asymmetry 2001, 12: 95

<A NAME="RU11303ST-10B">10b</A> Liu ZS. Li WDZ. Peng LZ. Li Y. Li YL. J. Chem. Soc., Perkin Trans. 1 2000, 4250

<A NAME="RU11303ST-10C">10c</A> Li YL. Liu ZS. Lan J. Li J. Peng LZ. Li WDZ. Li Y. Chan ASC. Tetrahedron Lett. 2000, 41: 7465

<A NAME="RU11303ST-10D">10d</A> Lan J. Liu ZS. Yuan H. Peng LZ. Li WDZ. Li Y. Li YL. Chan ASC. Tetrahedron Lett. 2000, 41: 2181

Data of pseudoplexaurol (2): [α]_D ²⁰ -19.5 (c 0.40, CHCl₃).
IR (film): ν_max = 3413 (brs), 2924, 2855, 1647, 1449, 1381, 1031, 898 cm^-1. LRMS (EI): m/z (%) = 304 (M, 0.9), 286 (2.8), 273 (7.2), 255 (4.9), 215 (7.2), 201 (8.3), 189 (12), 173 (15), 161 (27), 147 (39), 133 (78), 119 (70), 107 (77), 93 (90), 81 (100), 79 (77), 67 (87), 55 (67), 43 (55), 41 (59). ¹H NMR (400 MHz, CDCl₃): δ = 5.14 (1 H, d, J = 1.0 Hz, CH=), 5.06 (1 H, t, J = 6.4 Hz, CH=), 5.05 (1 H, dd, J = 6.4 Hz, CH=), 4.96 (1 H, d, J = 1.4 Hz, CH=), 4.11 (2 H, s, CH₂O), 2.65 (1 H, dd, J = 3.7, 7.0 Hz, epoxy H), 2.25-2.00 (11 H, m, 5 CH₂, CH), 1.72-1.52 (4 H, m, 2 CH₂), 1.63 (3 H, s, CH₃), 1.59 (3 H, s, CH₃), 1.22 (3 H, s, CH₃). HRMS (ESI) calcd for C₂₀H₃₂O₂Na: 327.2295. Found for [M + Na]⁺: 327.2295.

<A NAME="RU11303ST-12">12</A> Corey EJ. Gilman NM. Ganem BE. J. Am. Chem. Soc. 1968, 90: 5616

Data of 14-deoxycrassin (1): [α]_D ²⁰ +21 (c 0.06, CHCl₃).
IR (film): ν_max = 3393 (brs), 2928, 2851, 1726, 1642, 1437, 1382, 1105, 1065, 906 cm^-1. LRMS (EI): m/z (%) = 318 (M, 14), 300 (M - 18, 43), 285 (25), 272 (14), 257 (18), 247 (9), 243 (14), 229 (22), 215 (21), 193 (82), 175 (52), 161 (41), 147 (66), 133 (55), 121 (69), 107 (73), 93 (73), 81 (100), 79 (68), 67 (22), 55 (48), 53 (46), 43 (44). ¹H NMR (400 MHz, CDCl₃): δ = 6.58 (1 H, s, CH=), 5.76 (1 H, s, 1 H), 5.19 (1 H, t, J = 6.5 Hz, CH=), 5.07 (1 H, t, J = 6.4 Hz, CH=), 4.48 (1 H, d, J = 11.5 Hz, CHO), 2.74-2.67 (1 H, m, CH), 2.55-2.48 (2 H, m, CH₂), 2.16-2.06 (6 H, m, 3 CH₂), 1.95-1.81 (4 H, m, 2 CH₂), 1.76 (3 H, s, CH₃), 1.72 (3 H, s, CH₃), 1.46-1.40 (2 H, m, CH₂), 1.25 (3 H, s, CH₃). HRMS (ESI) calcd for C₂₁H₃₂O₃Na: 341.2087. Found for [M + Na]⁺: 341.2082.