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

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.

14-deoxycrassin - diterpenoids - cembranoids - total synthesi­s

References

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11

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.

12 Corey EJ. Gilman NM. Ganem BE. J. Am. Chem. Soc.  1968,  90:  5616 

13

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.