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Synlett 2011(18): 2652-2656  
DOI: 10.1055/s-0031-1289533
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Enantiospecific Approach to Tetraquinane Diterpenes Crinipellins: Synthesis of Norcrinipellins

A. Srikrishna*, V. Gowri
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
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Publication History

Received 4 July 2011
Publication Date:
19 October 2011 (online)

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Abstract

An enantiospecific approach to the synthesis of tetraquinane diterpene crinipellins is described. The cyclopentane ring in campholenaldehyde was identified as the B ring. Two rhodium carbenoid CH insertion reactions for the construction of A and C rings and an intramolecular Michael addition reaction for the D ring of crinipellins were employed as key strategies for the enantiospecific synthesis of norcrinipellins.

Key words

crinipellins - tetraquinanes - enantiospecific synthesis - campholenaldehyde - intramolecular Michael addition

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12

Yields refer to isolated and chromatographically pure compounds. All the compounds exhibited spectroscopic data (IR, ¹H and ¹³C NMR and HRMS) consistent with their structures. Spectroscopic data for (1R,2S,6R,8S,10R)-10-methoxy-2-methyltricyclo[6.3.0.0²,6]undec-3-en-5-one (19): [α]D ²¹ -76.8 (c 4.6, CHCl3); IR (neat): 1710, 1589, 1366, 1342, 1265, 1185, 1110, 1004, 836, 817, 784 cm-¹; ¹H NMR (300 MHz, CDCl3): δ = 7.39 (d, J = 5.4 Hz, 1 H, H-3), 6.02 (d, J = 5.4 Hz, 1 H, H-4), 3.83 (tt, J = 8.7, 6.3 Hz, 1 H, H-10), 3.28 (s, 3 H, OCH3), 2.36 (dd, J = 9.9, 1.5 Hz, 1 H, H-6), 2.25-1.90 (m, 6 H), 1.59 (dd, J = 11.4, 8.1 Hz, 1 H), 1.46 (dd, J = 13.5, 5.1 Hz, 1 H), 1.29 (s, 3 H, tert-CH3); ¹³C NMR (100 MHz, CDCl3): δ = 212.8 (C, C=O), 172.0 (CH, C-3), 131.3 (CH, C-4), 83.7 (CH, C-10), 58.0 (CH, C-6), 57.0 (CH3, OCH3), 55.1 (C, C-2), 49.5 (CH, C-1), 40.9 (CH, C-8), 37.0 (CH2), 36.1 (CH2), 33.5 (CH2), 21.5 (CH3, tert-CH3); HRMS: m/z calcd for C13H18O2Na [M + Na]: 229.1205; found: 229.1208.
(1R,2S,6S,8S,10R)-6-Allyl-10-methoxy-2,5-dimethyl-tricyclo[6.3.0.0²,6]undec-4-en-3-one (23): [α]D ²5 -29.8
(c 3.5, CHCl3); IR (neat): 1701, 1622, 1374, 1285, 1111, 995, 915, 865 cm-¹; ¹H NMR (300 MHz, CDCl3): δ = 5.91 (s, 1 H, H-4), 5.60 (ddt, J = 16.8, 9.9, 7.2 Hz, 1 H, CH=CH2), 5.06 (dd, J = 16.7, 1.8 Hz, 1 H, CH=CH 2), 5.01 (dd, J = 9.9, 1.8 Hz, 1 H, CH=CH 2), 3.78 (tt, J = 8.4, 5.7 Hz, 1 H, H-10), 3.28 (s, 3 H, OCH3), 2.50-2.37 (m, 2 H), 2.26 (dt, J = 12.0, 7.5 Hz, 1 H), 2.15-1.85 (m, 4 H), 2.02 (s, 3 H, olefinic CH3), 1.69-1.55 (m, 1 H), 1.49 (dd, J = 15.3, 8.4 Hz, 1 H), 1.41 (dd, J = 15.3, 4.5 Hz, 1 H), 1.09 (s, 3 H, tert-CH3); ¹³C NMR (100 MHz, CDCl3): δ = 212.9 (C, C=O), 180.4 (C, C-5), 134.6 (CH, CH=CH2), 130.2 (CH, C-4), 117.6 (CH2, CH=CH2), 83.2 (CH, C-10), 61.6 (C, C-2), 59.0 (C, C-6), 57.0 (CH3, OCH3), 51.1 (CH, C-1), 41.7 (CH2), 39.0 (CH2), 37.8 (CH, C-8), 35.7 (CH2), 33.5 (CH2), 15.6 (CH3), 15.4 (CH3); HRMS: m/z calcd for C17H24O2Na [M + Na]: 283.1674; found: 283.1662.
Ethyl 4-[(1R,2S,6S,8S,10R)-10-methoxy-2,5-dimethyl-3-oxotricyclo[6.3.0.0²,6]undec-4-en-6-yl]but-2-enoate (25): [α]D ²0 -60.6 (c 3.3, CHCl3); IR (neat): 1713, 1704, 1652, 1622, 1460, 1442, 1370, 1269, 1219, 1184, 1099, 1039, 977, 867 cm-¹; ¹H NMR (400 MHz, CDCl3): δ = 6.67 (dt, J = 15.6, 7.9 Hz, 1 H, H-3), 5.89 (s, 1 H, H-4′), 5.78 (d, J = 15.6 Hz, 1 H, H-2), 4.09 (q, J = 7.1 Hz, 2 H, OCH 2CH3), 3.80-3.65 (m, 1 H, H-10′), 3.21 (s, 3 H, OCH3), 2.52 (dd, J = 15.8, 6.5 Hz, 1 H, H-4), 2.45 (dd, J 15.7, 8.2 Hz, 1 H, H-4), 2.27-2.20 (m, 2 H), 2.15-1.75 (m, 3 H), 1.96 (s, 3 H, olefinic-CH3), 1.61 (t, J = 12.4 Hz, 1 H), 1.47-1.34 (m, 2 H), 1.21 (t, J = 7.1 Hz, 3 H, OCH2CH 3), 1.01 (s, 3 H, tert-CH3); ¹³C NMR (100 MHz, CDCl3): δ = 212.3 (C, C=O), 179.2 (C, C-5′), 165.6 (C, OC=O), 144.6 (CH, C-3), 130.7 (CH, C-4′), 123.9 (CH, C-2), 83.1 (CH, C-10′), 61.3 (C, C-2′), 60.2 (CH2, OCH2CH3), 59.3 (C, C-6′), 57.0 (CH3, OCH3), 51.1 (CH, C-1′), 41.6 (CH2), 37.9 (CH, C-8′), 37.6 (CH2), 35.6 (CH2), 33.6 (CH2), 15.9 (CH3), 15.5 (CH3), 14.2 (CH3); HRMS: m/z calcd for C20H28O4Na [M + Na]: 355.1886; found: 355.1894.
2-[(1S,3S,5R,7R,8S,11S,12R)-5-Methoxy-8,11-dimethyl-9-oxotetracyclo[6.6.0.0¹,¹¹.0³,7]tetradecan-12-yl]propan-2-ol (28x, norcrinipellin): m.p. 118-119 ˚C; [α]D ²4 -64.6 (c 1.4, CHCl3); IR (KBr): 3473 (OH), 2959, 2880, 1731 (C=O), 1460, 1373, 1225, 1108, 949 cm-¹; ¹H NMR (400 MHz, CDCl3): δ = 3.77 (tt, J = 8.4, 6.4 Hz, 1 H, H-5), 3.29 (s, 3 H, OCH3), 2.75 (d, J = 17.8 Hz, 1 H, H-10A), 2.37-2.15 (m, 2 H), 2.14 (d, J = 17.8 Hz, 1 H, H-10B), 2.15-1.90 (m, 4 H), 1.86-1.30 (m, 8 H), 1.32 (s, 3 H, tert-CH3), 1.22 (s, 3 H, tert-CH3), 1.20 (s, 3 H, tert-CH3), 1.12 (s, 3 H, tert-CH3); ¹³C NMR (100 MHz, CDCl3): δ = 224.4 (C, C=O), 82.9 (CH, C-5), 72.9 (C, C-OH), 65.9 (C, C-1), 60.8 (C, C-8), 57.3 (CH3, OCH3), 57.2 (CH, C-12), 53.6 (CH, C-7), 52.0 (CH2), 49.4 (C, C-11), 43.5 (CH2), 39.5 (CH, C-3), 37.1 (CH2), 34.3 (CH2), 33.0 (CH2), 31.3 (CH3) and 30.2 (CH3) [2 × tert-CH3], 25.0 (CH2), 18.9 (CH3) and 17.8 (CH3) [2 × tert-CH3]; HRMS: m/z calcd for C20H32O3Na [M + Na]: 343.2250; found: 343.2238; Anal. Calcd. for C20H32O3: C, 74.96; H, 10.06. Found: C, 74.95; H, 10.17.
2-[(1S,3S,5R,7R,8S,11S,12S)-5-Methoxy-8,11-dimethyl-9-oxotetracyclo[6.6.0.0¹,¹¹.0³,7]tetradecan-12-yl]propan-2-ol (28n, 12-epinorcrinipellin): [α]D ²³ +4.0 (c 1.0, CHCl3); IR (neat): 3469, 1729, 1371, 1257, 1220, 1113, 942 cm-¹; ¹H NMR (400 MHz, CDCl3): δ = 3.77 (quint., J = 7.3 Hz, 1 H, H-5), 3.28 (s, 3 H, OCH3), 3.19 (d, J = 17.0 Hz, 1 H, H-10A), 2.48 (dt, J = 12.0, 7.6 Hz, 1 H), 2.26 (dd, J = 13.8, 6.8 Hz, 1 H), 2.20-2.04 (m, 2 H), 2.00 (d, J = 17.0 Hz, 1 H, H-10B), 2.05-1.90 (m, 2 H), 1.80-1.65 (m, 2 H), 1.64 (dd,
J = 10.9, 6.3 Hz, 1 H), 1.55-1.35 (m, 5 H), 1.32 (s, 3 H, tert-CH3), 1.24 (s, 3 H, tert-CH3), 1.21 (s, 3 H, tert-CH3), 1.02 (s, 3 H, tert-CH3); ¹³C NMR (100 MHz, CDCl3): δ = 222.6 (C, C=O), 83.5 (CH, C-5), 72.6 (C, C-OH), 65.4 (C, C-1), 59.1 (CH, C-12), 59.0 (C, C-8), 57.1 (CH3, OCH3), 50.3 (CH, C-7), 47.1 (C, C-11), 46.8 (CH2), 45.7 (CH2), 40.0 (CH, C-3), 37.3 (CH2), 34.9 (CH2), 33.6 (CH2), 31.7 (CH3), 30.8 (CH3), 27.2 (CH2), 27.1 (CH3), 17.2 (CH3); HRMS: m/z calcd for C20H32O3Na [M + Na]: 343.2250; found: 343.2241.
(1S,3S,5R,7R,8S,11S,12S)-12-Isopropenyl-5-methoxy-8,11-dimethyltetracyclo[6.6.0.0¹,¹¹.0³,7]tetradecan-9-one (31x): [α]D ²² -22.5 (c 0.4, CHCl3); IR (neat): 1733, 1637, 1376, 1257, 1223, 1192, 1117, 891 cm-¹; ¹H NMR (400 MHz, CDCl3): δ = 4.86 (s, 1 H, C=CH2), 4.68 (s, 1 H, C=CH2), 3.77 (quint., J = 7.0 Hz, 1 H, H-5), 3.29 (s, 3 H, OCH3), 2.56 (d, J = 17.8 Hz, 1 H, H-10A), 2.34-2.25 (m, 2 H), 2.17-1.75 (m, 6 H), 1.73 (s, 3 H, olefinic CH3), 1.74-1.60 (m, 3 H), 1.51-1.40 (m, 2 H), 1.31 (dd, J = 11.0, 6.8 Hz, 1 H), 1.10 (s, 3 H, tert-CH3), 0.93 (s, 3 H, tert-CH3); ¹³C NMR (100 MHz, CDCl3): δ = 223.6 (C, C=O), 144.3 (C, C=CH2), 113.3 (CH2, C=CH2), 83.0 (CH, C-5), 64.7 (C, C-1), 61.2 (C, C-8), 57.2 (CH3, OCH3), 56.3 (CH, C-12), 52.9 (CH, C-7), 50.5 (CH2, C-10), 49.5 (C, C-11), 44.6 (CH2), 39.7 (CH, C-3), 37.1 (CH2), 34.1 (CH2), 33.7 (CH2), 27.4 (CH2), 23.4 (CH3), 18.3 (CH3), 18.1 (CH3); HRMS: m/z calcd for C20H30O2Na [M + Na]: 325.2145; found: 325.2139.
(1S,3S,5R,7R,8S,11S,12R)-12-Isopropenyl-5-methoxy-8,11-dimethyltetracyclo[6.6.0.0¹,¹¹.0³,7]tetradecan-9-one (31n): [α]D ²4 -60.0 (c 0.6, CHCl3); IR (neat): 1732, 1637, 1377, 1261, 1223, 1191, 1115, 1019, 891, 801 cm-¹; ¹H NMR (400 MHz, CDCl3): δ = 4.86 (s, 1 H, C=CH2), 4.69 (s, 1 H, C=CH2], 3.77 (quint., J = 7.3 Hz, 1 H, H-5), 3.28 (s, 3 H, OCH3), 2.55-2.40 (m, 1 H), 2.45 (d, J = 17.1 Hz, 1 H, H-10A), 2.17-2.00 (m, 4 H), 2.00-1.88 (m, 2 H), 1.87 (d,
J = 17.1 Hz, 1 H, H-10B), 1.74 (s, 3 H, olefinic CH3), 1.66-1.60 (m, 1 H), 1.53-1.40 (m, 4 H), 1.31 (dd, J = 11.0, 6.8 Hz, 1 H), 1.18 (s, 3 H, tert-CH3), 1.02 (s, 3 H, tert-CH3]; ¹³C NMR (100 MHz, CDCl3): δ = 221.7 (C, C=O), 144.8 (C, C=CH2), 112.9 (CH2, C=CH2), 83.6 (CH, C-5), 64.2 (C, C-1), 59.6 (C, C-8), 57.3 (CH3, OCH3), 57.1 (CH, C-12), 50.6 (CH, C-7), 47.3 (C, C-11), 46.4 (CH2, C-10), 45.7 (CH2), 40.1 (CH, C-3), 37.2 (CH2), 34.8 (CH2), 33.5 (CH2), 29.5 (CH2), 25.1 (CH3), 23.9 (CH3), 16.9 (CH3); HRMS: m/z calcd for C20H30O2Na [M + Na]: 325.2145; found: 325.2140.
Crystal data for norcrinipellin (28x): X-ray data were collected at 296 K with a SMART CCDBRUKER diffractometer with graphite-monochromated MoKα radiation (0.71073 Å). The structure was solved by direct methods (SIR 92). Refinement was by full-matrix least-squares procedures on F2 using SHELXL-97. The nonhydrogen atoms were refined anisotropically, whereas hydrogen atoms were refined isotropically. Molecular formula C20H32O3; MW = 320.5; T = 296 (2) K; Crystal system: monoclinic; Space group: P21; cell parameters: a = 9.5828 (4) Å; b = 8.1659 (4) Å; c = 11.7728 (5) Å; α = 90 (0)˚; β = 101.3 (3)˚; γ = 90 (0)˚; V = 903.6 (7) ų; Z = 2; D calcd = 1.18 g˙cm-³; F(000) = 352; µ = 0.077 mm-¹; Total number of l.s. parameters = 212; R: = 0.068 for 1789
[I > 2σ(I)]; wR2 = 0.216 and 0.0961 for all 12211 data; GOF = 1.019; Restrained GOF = 1.019 for all data; An ORTEP diagram is depicted in Figure  [²] . Crystallographic data have been deposited with the Cambridge Crystallographic Data Centre (CCDC 831696).