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Synlett 2011(5): 647-650  
DOI: 10.1055/s-0030-1259551
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthetic Study on Sespendole, an Indole Sesquiterpene Alkaloid: Stereo­controlled Synthesis of the Sesquiterpene Segment Bearing All Requisite Stereogenic Centers

Kumi Sugino, Atsuo Nakazaki, Minoru Isobe, Toshio Nishikawa*
Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan
Fax: +81(52)7894111; e-Mail: nisikawa@agr.nagoya-u.ac.jp;
Further Information

Publication History

Received 16 December 2010
Publication Date:
11 February 2011 (online)

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Abstract

Stereocontrolled synthesis of a sesquiterpene segment with all requisite stereogenic centers for sespendole has been achieved. Synthetic features of our strategy involve (1) highly stereoselective [2,3]-Wittig rearrangement to obtain sterically congested quaternary carbon and (2) isomerization of a spiro epoxide into aldehyde with Cp2TiCl2/Mn in a highly stereoselective manner.

Key words

natural product synthesis - sespendole - indole sesqui­terpene - [2,3]-Wittig rearrangement - isomerization

    References and Notes

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8

All new compounds were fully characterized by ¹H NMR, ¹³C NMR, and IR analyses.
Data for Selected Compounds
Alcohol 12: IR (film): νmax = 3362, 2954, 2856, 1635, 1472, 1253, 1063, 835 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 0.04 (3 H, s, CH3 of TBS), 0.05 (3 H, s, CH3 of TBS), 0.24 (9 H, s, CH3 of TMS), 0.88 (9 H, s, CH3 of t-Bu), 1.02 (3 H, s, CCH 3axCH3eq), 1.02 (3H, s, CCH3axCH 3eq), 1.04 (3 H, s, CCH3), 1.29 [3 H, s, C(CH2OH)CH 3], 1.29 (1 H, dt, J = 12.0, 3.5 Hz, CHbHcCHd H e), 1.55-1.63 (2 H, m, CHaCH b H c), 1.77 (1 H, ddd, J = 14.0, 6.5, 4.5 Hz, CHhHiCH jHk), 1.82 (1 H, ddd, J = 14.0, 10.0, 6.0 Hz, CHhHiCHj H k), 2.09 (1 H, ddd, J = 13.0, 10.0, 8.0 Hz, CHbHcCH dHe), 2.22 (1 H, dddd, J = 13.5, 6.0, 4.5, 1.0 Hz, CHh H iCHjHk), 2.46 (1 H, dddt, J = 13.5, 10.0, 6.5, 1.0 Hz, CH hHiCHjHk), 3.57 (1 H, br d, J = 11.0 Hz, CH xHyOH), 3.68 (1 H, d, J = 11.0 Hz, CHx H yOH), 3.77 (1 H, dd, J = 9.5, 7.0 Hz, TBSOCHa), 4.71 (1 H, br s, H mHnC=C), 4.89 (1 H, br s, Hm H nC=C). ¹³C NMR (100 MHz, CDCl3): δ = -4.7, -3.8, 4.5, 18.1, 19.2, 20.2, 22.7, 25.9, 26.1, 27.6, 28.4, 28.7, 29.9, 46.2, 46.5, 48.4, 68.0, 74.1, 88.9, 108.4, 152.6. ESI-HRMS: m/z calcd for C25H50O3Si2Na [M + Na]: 477.3191; found: 477.3202.
Alcohol 2: IR (film): νmax = 3311, 2955, 2103, 1253, 1097, 1006, 836 cm-¹. ¹H NMR (600 MHz, CDCl3): δ = 0.03 (3 H, s, CH3 of TBS) 0.04 (3 H, s, CH3 of TBS), 0.21 (9 H, s, CH3 of TMS), 0.87 (9 H, s, CH3 of t-Bu), 0.95 (3 H, s, CCH3CH 3), 1.00 (3 H, s, CCH 3CH3), 1.26 (3 H, s, CCH3), 1.33 (1 H, dt, J = 13.0, 3.5 Hz, CHbHcCHd H e), 1.35 (1 H, td, J = 13.5, 4.0 Hz, CHgCH hHi), 1.41 (3 H, s, CCH3), 1.60-1.69 (3 H, m, CHaCH b H c, CHhHiCH jHk), 1.72 (1 H, dq, J = 13.5, 3.5 Hz, CHgCHh H i), 1.81 (1 H, td, J = 14.0, 4.0 Hz, CHhHiCHj H k), 2.05 (1 H, td, J = 13.0, 5.0 Hz, CHbHcCH dHe), 2.08 (1 H, tt, J = 12.5, 4.0 Hz, HOCH2CH g), 2.20 (1 H, s, CºCH), 3.41 (1 H, br s, HOCH xHyCHg), 3.75 (1 H, dd, J = 11.0, 6.0 Hz, TBSOCHa), 4.03 (1 H, dd, J = 10.5, 5.0 Hz, HOCHx H yCHg). ¹³C NMR (100 MHz, CDCl3): δ = -4.7, -3.7, 4.5, 18.0, 19.9, 21.4, 21.5, 22.4, 25.1, 25.8, 26.0, 26.3, 28.5, 42.9, 44.6, 45.1, 46.2, 66.0, 71.2, 73.9, 87.5, 92.7. ESI-HRMS: m/z calcd for C26H50O3Si2Na [M + Na]: 489.3191; found: 489.3210.

16

Relevant 1,4-addition of α,β-unsaturated ketone, derived from 3 (vide supra) with Me2CuLi, was also examined; however, only 1,2-addition product was obtained. Therefore we concluded that this sort of α,β-unsaturated carbonyl compounds would be unreactive due to their steric hindrance.

24

This reaction did not proceed with Cp2TiCl2 as a Lewis acid. When the Lewis acid such as MgBr2˙OEt2, BF3˙OEt2, or AlCl3 was used for this conversion, the reaction provide lower yield of the desired aldehyde.