A Short and Efficient Preparation of Enantiopure Secosyrins 1 and 2

Abstract

An alternative, short and efficient approach for the preparation of enantiopure secosyrins 1 and 2 is reported here. This uses a d-arabinose derivative as starting material and applies a HWE-IHMA strategy for the construction of the spiro-framework of target molecules.

secosyrins - d-arabinose - HWE olefination - Michael addition - total synthesis

References and Notes

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Preliminary results of this work were presented at the 1^st European Chemistry Congress, Budapest, Hungary, August 2006, p. 329 (N-PO-94).

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Compounds 5 and 6 have been previously prepared from d-mannitol, following an alternative synthetic scheme:

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<A NAME="RG24906ST-14A">14a</A>

Compound 10: oil; [α]_D ²⁵ -48.3 (c 1.6, CHCl₃). IR (neat): 3032, 2987, 2936, 2890, 1780, 1641, 1455, 1372, 1259, 1213, 1071, 1029, 888, 852, 739, 700 cm^-1. ¹ H NMR (300 MHz, CDCl₃): δ = 7.39-7.30 (m, 5 H), 6.07 (s, 1 H), 4.93 and 4.85 (dABq, J = 18.0, 1.8 Hz, 2 H), 4.67 and 4.51 (ABq, J = 12.2 Hz, 2 H), 4.43 (d, J = 4.9 Hz, 1 H), 4.33 (ddd, J = 7.0, 6.1, 4.9 Hz, 1 H), 4.03 (dd, J = 8.6, 7.0 Hz, 1 H), 3.82 (dd, J = 8.6, 6.1 Hz, 1 H), 1.40 (s, 3 H), 1.34 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 172.9, 166.6, 136.7, 128.7, 128.3, 127.9, 118.6, 110.1, 76.10, 75.2, 72.5, 72.1, 65.2, 26.0, 24.9. HRMS (MALDI-FTMS): m/e calcd for C₁₇H₂₀O₅Na [M + Na]⁺: 327.1208; found: 327.1207.

<A NAME="RG24906ST-14B">14b</A>

Compound 14: oil; [α]_D ²⁵ -5.3 (c 0.8, MeOH). IR (neat): 3445, 2930, 2910, 1779, 1456, 1398, 1207, 1077, 1012, 741, 699 cm^-1. ¹ H NMR (300 MHz, CDCl₃): δ = 7.40-7.31 (m, 5 H), 4.76 and 4.60 (ABq, J = 12.2 Hz, 2 H), 4.45-4.41 (m, 1 H), 4.37 and 4.28 (ABq, J = 10.4 Hz, 2 H), 4.11 (dd, J = 10.4, 4.9 Hz, 1 H), 3.83 (dd, J = 10.4, 2.5 Hz, 1 H), 3.82 (d, J = 1.8 Hz, 1 H), 2.98 and 2.56 (ABq, J = 18.3 Hz, 2 H), 2.74 (br s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 175.7, 137.1, 128.7, 128.2, 127.7, 87.4, 86.2, 76.5, 74.7, 73.3, 72.5, 35.4. HRMS (MALDI-FTMS): m/e calcd for C₁₄H₁₆O₅Na [M + Na]⁺: 287.0895; found: 287.0894.

<A NAME="RG24906ST-15">15</A> Wang ES. Choy YM. Wong HNC. Tetrahedron  1996,  52:  12137 

<A NAME="RG24906ST-16">16</A>

The 3-O-TBS derivative instead of the 3-O-benzyl derivative (12).

<A NAME="RG24906ST-17">17</A>

Compound 15 was found to have identical physical and spectra data with those reported in ref. 7c.

<A NAME="RG24906ST-18">18</A>

Compounds 2a and 2b were found to have physical and spectral data identical to those reported in ref. 7a.

<A NAME="RG24906ST-19">19</A>

To the best of our knowledge, these are the highest overall yields reported so far for the total synthesis of both secosyrins.