Total Synthesis of Achaetolide
from d-Mannitol

K. Sripad Rao; Amit Kumar Chattapadhyay; Subhash Ghosh

doi:10.1055/s-0030-1259056

LETTER

Total Synthesis of Achaetolide from d-Mannitol

K. Sripad Rao, Amit Kumar Chattapadhyay, Subhash Ghosh*
Organic Chemistry Division III, Indian Institute of Chemical Technology, Hyderabad 500607, India
Fax: +91(40)27193108; e-Mail: subhash@iict.res.in;

Abstract

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Abstract

A highly convergent stereoselective total synthesis of achaetolide, a ten-membered lactone is described. The ring-closing metathesis reaction was used to construct the macrocycle and E-olefinic moiety in the molecule. The key acid and alcohol fragments were synthesized from a single chiral pool material d-mannitol.

Key words

Achaetominum cristalliferum - Ophiobolus sp. - achaetolide - d-mannitol - ring-closing metathesis

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References

References and Notes

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Analytical data for 5: [α]^²5 _D -30.3 (c = 0.82, CHCl₃). ^¹H NMR (300 MHz, CDCl₃): δ = 7.24-7.30 (m, 4 H), 7.19 (d, J = 8.4 Hz, 2 H), 6.84-6.90 (m, 4 H), 6.78 (d, J = 8.4 Hz, 2 H), 5.73-5.86 (m, 2 H), 5.23-5.36 (m, 5 H), 4.59 (d, J = 11.7 Hz, 1 H), 4.49 (d, J = 10.95 Hz, 1 H), 4.47 (d, J = 10.0 Hz, 1 H), 4.25-4.37 (m, 4 H), 3.82 (m, 1 H), 3.81 (s, 3 H), 3.80 (s, 3 H), 3.75 (s, 3 H), 3.48 (m, 1 H), 2.67 (dd, J = 15.3, 8.1 Hz, 1 H), 2.48 (dd, J = 15.3, 5.3 Hz, 1 H), 1.65-1.74 (m, 3 H), 1.45-1.56 (m, 2 H), 1.21-1.30 (br s, 9 H), 0.88 (t, J = 6.7 Hz, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 170.6, 159.2, 159.1, 137.5, 135.8, 130.9, 130.7, 130.4, 130.0, 129.3, 118.9, 118.1, 113.7, 81.1, 78.0, 77.5, 76.9, 72.9, 71.6, 70.2, 70.1, 55.3, 41.3, 35.9, 35.2, 31.8, 29.6, 29.2, 25.2, 22.7, 14.1. IR: 2926, 2858, 1730, 1512, 1246, 1034 cm^-¹. MS (ESI): m/z = 711 [M + Na]⁺. HRMS (ESI): m/z [M + Na]⁺ calcd for C₄₂H₅₆O₈Na: 711.3872; found: 711.3884.

Analytical data of achaetolide (1): mp 122-124 ˚C; [α]^²5 _D -22 (c = 0.1, MeOH); {lit.^²a [α]^²5 _D -27 (c = 0.52, MeOH)}. ^¹H NMR (300 MHz, CDCl₃): δ = 6.02 (ddd, J = 15.8, 3.02, 2.26 Hz, 1 H), 5.68 (dd, J = 15.8, 2.3 Hz, 1 H), 4.82 (q, J = 6.8 Hz, 1 H), 4.75 (m, 1 H), 4.57 (m, 1 H), 3.77 (d, J = 9.8 Hz, 1 H), 2.62 (dd, J = 12.1, 3.0 Hz, 1 H), 2.57 (dd, J = 12.1, 3.7 Hz, 1 H), 2.34 (ddd, J = 15.1, 10.5, 8.3 Hz, 1 H), 2.17 (br s, 2 H, OH), 2.03 (br s, 1 H, OH), 1.53-1.68 (m, 2 H), 1.48 (d, J = 15.8 Hz, 1 H), 1.21-1.31 (m, 10 H), 0.87 (t, J = 6.7 Hz, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 171.0, 130.8, 125.1, 75.3, 73.2, 67.1, 43.8, 36.9, 36.8, 31.7, 29.6, 29.3, 29.1, 24.9, 22.6, 14.0. IR: 2923, 2854, 1739, 1709, 1647, 1513, 1372, 1171 cm^-¹. MS (ESI): m/z = 323 [M + Na]⁺.

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