Synthesis of Δ²-OPC-8:0 and OPC-6:0

Abstract

Δ²-OPC-8:0 (6), designed as a β-oxidation-insensitive analogue, was synthesized starting with 4-cyclopentene-1,3-diol monoacetate (5) in a stereocontrolled manner. The C(3)-C(8) ­moiety was first attached to the cyclopentene ring by using the Cu-catalyzed S_N2-type reaction with TBDPSO(CH₂)₆MgCl and was later converted into the full side chain by Wittig reaction. In ­addition, OPC-6:0 (3) was synthesized.

allylations - asymmetric synthesis - copper - cuprates - stereoselective synthesis

References

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<A NAME="RU20004ST-14">14</A>

Synthesis of 3-oxa analogue of 13-epi-OPC-8:0 methyl ester (trans isomer) in racemic form was reported: see ref. 4a.

<A NAME="RU20004ST-15">15</A> Sugai T. Mori K. Synthesis  1988,  19 

<A NAME="RU20004ST-16">16</A>

The conditions used here for the selective desilylation are also successful in other cases.

<A NAME="RU20004ST-17">17</A>

Spectral data (¹H NMR at 300 MHz and ¹³C NMR at 75 MHz in CDCl₃) and specific rotations of the intermediates. Lactone 13: [α]_D ²⁴ -5.7 (c 0.53, CHCl₃). IR (neat): 1771, 1111 cm^-1. ¹H NMR: δ = 0.97 (s, 9 H), 1.10-1.36 (m, 10 H), 1.42-2.20 (m, 5 H), 2.35 (dd, J = 19, 6 Hz, 1 H), 2.42 (dd, J = 19, 10 Hz, 1 H), 2.78-2.92 (m, 1 H), 3.58 (t, J = 6 Hz, 2 H), 4.95 (t, J = 6 Hz, 1 H), 7.33- 7.43 (m, 6 H), 7.63-7.69 (m, 4 H). ¹³C NMR: d = 19.3, 25.7, 26.9, 28.5, 28.7, 28.9, 29.5, 30.6, 32.5, 33.1, 40.5, 42.8, 63.9, 86.2, 127.6, 129.6, 134.2, 135.6, 178.1. Ester 14: [α]_D ²³ +0.10 (c 1.98, CHCl₃). IR (neat): 1741, 1112 cm^-1. ¹H NMR: δ = 0.55 (q, J = 8 Hz, 6 H), 0.93 (t, J = 8 Hz, 9 H), 1.04 (s, 9 H), 1.08-1.93 (m, 15 H), 2.20 (dd, J = 15, 5.5 Hz, 1 H), 2.32-2.44 (m, 1 H), 2.46 (dd, J = 15, 7.5 Hz, 1 H), 3.64 (t, J = 6.5 Hz, 2 H), 3.65 (s, 3 H), 4.17-4.24 (m, 1 H), 7.33-7.43 (m, 6 H), 7.64-7.70 (m, 4 H). ¹³C NMR: δ = 4.9, 6.9, 19.3, 25.9, 26.9, 28.1, 28.4, 29.5, 29.7, 31.7, 32.7, 32.8, 39.6, 43.8, 51.4, 64.1, 75.0, 127.6, 129.6, 134.3, 135.7, 174.9. Olefin 15: [α]_D ²⁵ +2.2 (c 0.368, CHCl₃). IR (neat): 1428, 1112, 701 cm^-1. ¹H NMR: δ = 0.56 (q, J = 8 Hz, 6 H), 0.95 (t, J = 8 Hz, 9 H), 0.96 (t, J = 7.5 Hz, 3 H), 1.04 (s, 9 H), 1.15-1.88 (m, 16 H), 1.98-2.24 (m, 4 H), 3.65 (t, J = 6.5 Hz, 2 H), 4.06-4.19 (m, 1 H), 5.24-5.48 (m, 2 H), 7.34-7.43 (m, 6 H), 7.64-7.70 (m, 4 H). ¹³C NMR: δ = 5.0, 7.0, 14.4, 19.3, 20.8, 22.4, 25.9, 26.9, 28.5, 28.8, 29.8, 31.8, 32.7, 33.4, 39.9, 48.7, 64.1, 75.5, 127.6, 129.5, 129.9, 131.1, 134.3, 135.7. Diol 9: [α]_D ²⁴ +12 (c 0.388, CHCl₃). IR (neat): 3350, 1056 cm^-1. ¹H NMR: δ = 0.98 (t, J = 7.5 Hz, 3 H), 1.19-1.95 (m, 17 H), 2.20-2.50 (m, 5 H), 3.64 (t, J = 6.5 Hz, 2 H), 4.14-4.26 (m, 1 H), 5.34-5.49 (m, 2 H). ¹³C NMR: δ = 14.5, 20.9, 22.8, 25.9, 28.9, 29.1, 29.8, 31.8, 32.9, 33.2, 40.1, 47.9, 63.1, 75.5, 128.7, 132.1. Hydroxyl acid 20: IR (neat): 3410, 1699, 1652 cm^-1. ¹H NMR: δ = 0.96 (t, J = 7.5 Hz, 3 H), 1.13-2.44 (m, 21 H), 4.15-4.25 (m, 1 H), 5.22-5.51 (m, 2 H), 5.82 (d, J = 16 Hz, 1 H), 6.98-7.13 (dt, J = 16, 7 Hz, 1 H). ¹³C NMR: δ = 14.4, 20.8, 22.7, 28.0, 28.6, 29.0, 29.5, 31.7, 32.4, 33.1, 40.0, 47.8, 75.5, 120.8, 128.7, 132.3, 152.3, 171.8.

<A NAME="RU20004ST-18">18</A>

Both 3 and 24 appeared on TLC with the same R _f value.