Enantioselective total synthesis and assignment of the absolute configuration of (+)-laurokamurene B

doi:10.1016/j.tetasy.2008.02.010

Tetrahedron: Asymmetry

Volume 19, Issue 5, 18 March 2008, Pages 624-627

https://doi.org/10.1016/j.tetasy.2008.02.010 Get rights and content

Abstract

The first enantioselective total synthesis of the rearranged aromatic sesquiterpene (+)-laurokamurene B, isolated from the Chinese red algae Laurencia okamurai Yamada, has been accomplished starting from (S)-campholenaldehyde, establishing the absolute configuration of laurokamurenes.

Graphical abstract

Introduction

Over the last four decades, a significant number of cuparene and laurene sesquiterpenoids have been isolated from the genus Laurencia, which are characteristic of the genus.¹ Recently, Mao and Guo in the course of their investigations on the isolation of biologically active compounds from Chinese marine organisms reported the isolation of two new aromatic sesquiterpenes laurokamurenes A and B 1 and 2, containing a new rearranged laurane skeleton, along with known laurene sesquiterpenes 3–5.² The structures of laurokamurenes A and B 1 and 2 were established on the basis of 1 and 2D NMR spectra, however, their absolute configuration was not assigned. A large number of brominated and non-brominated sesquiterpenes, which can be classified into more than 20 sesquiterpenoid skeletons, are known from the red algae of the genus Laurencia. However, in most cases, three methyls in the aliphatic portion were located at either positions 1,2,3 (laurene type) or 1,2,2 (cuparene type).³ Laurokamurenes 1 and 2 were the first members of a new class of sesquiterpenes with three methyls in the aliphatic ring arranged in a 2,2,3 fashion.

The presence of a new sesquiterpene carbon framework prompted us to investigate the synthesis of laurokamurene B 2. Recently,⁴ we have accomplished the first total synthesis of laurokamurene B 2 employing a combination of an Ireland–Claisen rearrangement and RCM reactions establishing the structure of the marine natural product. Herein, we report the first enantioselective synthesis of (+)-laurokamurene B 2 establishing the absolute configuration of laurokamurenes. It was contemplated that the three methyl groups present on the vicinal carbons of campholenaldehyde 6 could be exploited for the enantioselective generation of laurokamurenes via 2,2,3-trimethylcyclopentanone 7 and the α,β-unsaturated ester 8 (Scheme 1).

Section snippets

Results and discussion

The synthetic sequence is depicted in Scheme 2. The requisite stereogenic centre of the laurokamurenes has been created by stereoselective hydrogenation. Thus, oxidation of campholenaldehyde 6 with Jones’ reagent followed by esterification of the resultant campholenic acid,⁵ generated methyl campholenate 9. Hydrogenation of campholenate 9 in hexane with 10% palladium over carbon as the catalyst furnished dihydrocampholenate 10 in a stereoselective manner (>95% by NMR) in near quantitative

Conclusion

In conclusion, we have accomplished the first enantioselective total synthesis of the sesquiterpene laurokamurene (+)-2, starting from (S)-campholenaldehyde 6, and established the absolute configuration of the laurokamurenes containing a new sesquiterpene carbon framework.

Experimental

IR spectra were recorded on a Jasco FTIR 410 spectrophotometer. ¹H (300 and 400 MHz) and ¹³C (75 and 100 MHz) NMR spectra were recorded on JEOL JNM λ-300 and Brucker Avance 400 spectrometers. The chemical shifts (δ ppm) and coupling constants (Hz) are reported in the standard fashion with reference to either internal tetramethylsilane (for ¹H) or the central line (77.0 ppm) of CDCl₃ (for ¹³C). In the ¹³C NMR, the nature of carbons (C, CH, CH₂, CH₃) was determined by recording the DEPT-135 spectra,

Acknowledgements

We thank the Department of Science and Technology, New Delhi for the financial support, Indian Institute of Science and University Grants Commission, New Delhi for the award of research fellowships to B.B. and R.R.B. We are grateful to M/s Organica Aromatics (Bangalore) Pvt. Ltd, for the generous gift of campholenaldehyde.

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