Synlett 2017; 28(20): 2928-2932
DOI: 10.1055/s-0036-1590858
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of (–)-Muricatacin and (–)-(R,R)-L-Factor Involving an Organocatalytic Direct Vinylogous Aldol Reaction

Christopher Cooze
Department of Chemistry, Memorial University, St. John’s, Newfoundland, A1B 3X7, Canada   Email: spansare@mun.ca
,
Amarender Manchoju
Department of Chemistry, Memorial University, St. John’s, Newfoundland, A1B 3X7, Canada   Email: spansare@mun.ca
,
Sunil V. Pansare*
Department of Chemistry, Memorial University, St. John’s, Newfoundland, A1B 3X7, Canada   Email: spansare@mun.ca
› Author Affiliations
Financial support from the Natural Sciences and Engineering Research Council of Canada and the Canada Foundation for Innovation is gratefully acknowledged. Christopher Cooze is the recipient of a NSERC Undergraduate Student Research Award.
Further Information

Publication History

Received: 13 June 2017

Accepted after revision: 07 July 2017

Publication Date:
14 August 2017 (eFirst)

Dedicated to Professor Victor Snieckus on the occasion of his 80th birthday

Abstract

Concise syntheses of the polyketide natural product (–)-muricatacin and (–)-(R,R)-L-factor (natural product enantiomer) were achieved in four steps by employing an organocatalytic asymmetric direct vinylogous aldol reaction of γ-crotonolactone and suitable aliphatic aldehydes as the key step.

Supporting Information

 
  • References and Notes

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      Selected syntheses:
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  • 17 See the Supporting Information for the solvent optimization studies with catalysts (R,R)-6 and 13.
  • 18 Of the diastereomers of 16 and 17, the specific rotation of only syn-16 is reported in the literature.8o In our studies, the separation of syn-16 and anti-16 by chromatography proved to be extremely difficult and diastereomerically pure syn-16 could not be obtained. Hence, the absolute configuration of the lactone stereocenter in 16 was assigned on the basis of our previous studies with aromatic aldehydes.16c The syn and anti dia­stereomers in 16 and 17 were assigned by comparison of the trend in chemical shift of their methine hydrogens with that reported for 16.15d These assignments were subsequently confirmed by the conversion of syn-16 into 1 and syn-17 into 3.
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  • 21 General Procedure for the Reduction of 20 and 21 To a solution of the ketone (1 equiv) in dry THF was added K-Selectride (1.5 equiv, 1 M in THF) at –78 °C, and the mixture was stirred at –78 °C for 1 h. Saturated NH4Cl (5 mL) was added at –78 °C, and the mixture was warmed to r.t. The mixture was then extracted with EtOAc (3 × 5 mL), and the combined extracts were dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography on silica gel. (R)-5-[(R)-1-Hydroxytridecyl]dihydrofuran-2(3H)-one – (–)-Muricatacin (1) The reaction of ketone 20 (50 mg, 0.18 mmol) and K-Selectride (0.27 mL, 0.27 mmol, 1.0 M in THF) in dry THF (1 mL) for 30 min according to the general procedure provided, after purification by flash chromatography on silica gel (CH2Cl2/EtOAc, 9:1), 37 mg (74%) of 1 as a white solid. Rf = 0.30 (CH2Cl2/EtOAc, 9:1); [α]D 23–18.6 (c 1.77, CH2Cl2), mp 65.5–69.1 °C; lit.8a [α]D 23–17.5 (c 1.0, CH2Cl2), mp 66–68 °C; lit.8o [α]D 23–19 (c 1.8, CH2Cl2), mp 68–70 °C. IR (neat): 3415(br), 2957, 2916, 2847, 1761, 1471, 1462, 1267, 1189, 1331, 1104, 1082, 1011 cm–1. 1H NMR (300 MHz, CDCl3): δ = 4.42 (td, 1 H, J = 7.3, 4.6 Hz, OCH), 3.58 (quint, 1 H, J = 5.3 Hz, CHOH), 2.69–2.46 (m, 2 H, CH2), 2.33–2.04 (m, 2 H, CH2), 1.95–1.85 [br m, 1 H, OH (D2O exchange)], 1.64–1.20 (m, 22 H, CH2), 0.88 (t, 3 H, J = 6.6 Hz, CH3). 13C NMR (75 MHz, CDCl3): δ = 177.2 (C(O)O), 83.0 (OCH), 73.7 (CHOH), 33.0 (CH2), 31.9 (CH2), 29.7 (CH2), 29.64 (2 × CH2), 29.58 (CH2), 29.51 (CH2), 29.50 (CH2), 29.4 (CH2), 28.7 (CH2), 25.5 (CH2), 24.1 (CH2), 22.7 (CH2), 14.1 (CH3). HRMS (ESI, pos): m/z calcd for C17H32O3 [M]+: 284.2351; found: 284.2340; m/z calcd for C17H33O3 [M + Na]+: 307.2249; found: 307.2232. (R)-5-[(R)-1-Hydroxyhexyl]dihydrofuran-2(3H)-one – (–)-L-Factor (3) The reaction of ketone 21 (60 mg, 0.33 mmol) and K-Selectride (0.48 mL, 0.49 mmol) in dry THF (2 mL) for 1 h according to the general procedure provided, after purification by flash chromatography on silica gel (CH2Cl2/EtOAc, 9:1), 48 mg (78%) of 3 as a white solid. Rf = 0.22 (CH2Cl2/EtOAc, 4:1); [α]D 23 –29.3 (c 1.27, CHCl3), mp 41–43 °C; lit.8a [α]D 25–27.1 (c 0.6, CHCl3), mp 42–44 °C; lit.8b [α]D 23 –32.8 (c 1.54, CHCl3), mp 45–48 °C. IR: 3450 (br), 2954, 2928, 2858, 1765, 1185, 1133, 1075, 1057, 1023, 992, 929, 907 cm–1. 1H NMR (300 MHz, CDCl3): δ = 4.42 (td, 1 H, J = 7.3, 4.4 Hz, OCH), 3.62–3.52 (br m, 1 H, CHOH), 2.69–2.46 (m, 2 H, CH2), 2.32–2.01 [m, 3 H, CH2, OH (D2O exchange)], 1.62–1.21 (m, 8 H, CH2), 0.89 (t, 3 H, J = 6.7 Hz, CH3). 13C NMR (75 MHz, CDCl3): δ = 177.3 (C(O)O), 83.0 (OCH), 73.6 (CHOH), 32.9 (CH2), 31.7 (CH2), 28.7 (CH2), 25.1 (CH2), 24.1 (CH2), 22.5 (CH2), 14.0 (CH3). HRMS (APPI, pos): m/z calcd for C10H18O3 [M]+: 186.1256; found: 186.1252; m/z calcd for C10H19O3 [M + H]+: 187.1334; found: 187.1325.