In the Quest for a Virtual Pseudo Receptor for Sandalwood‐Like Odorants. Part I

Abstract

Based on similarities between naturally occurring (-)-(Z)-beta- or (+)-(Z)-alpha-santalol ((-)- 1 or (+)-2, resp.) and the reversed (E)-configured synthetic derivatives from campholenal (7a), a simple model A was developed. Besides reconciliation of this stereochemical aspect, this initial model also tentatively explained the enantiodiscriminations as well as the large spectra of distances separating the OH function from the lipophilic quaternary center(s) reported for different classes of substrates. Evolution, modifications, and refinement of this imperfect model allied with the research for alternative possibilities are illustrated, along with a historical guideline, in the light of olfactively challenging synthetic seco-substructures as well as literature reports. Despite evolution of the inadequate model A and a plausible interpretation of the lipophilic part, the topological positions of the OH function and its vicinal alkyl substituent could nevertheless not be fully ascertained by this approach. This apparently inconclusive empirical concept prompted us to turn our attention towards a computerized methodology, which will constitute the second and third part of this study.

Structure-Odor Relationships of α­Santalol Derivatives with Modified Side Chains

“…The odor of Z -isomer 4 was sandalwood-like and found to be different from that of E -isomer 5 (slightly fatty). A similar result has been reported previously [ 10 ]. The Z -isomer of α-santalol has sandalwood odor, but the E -isomer does not.…”

The Synthesis of Fragrant Natural Products from Santalum album L.: (+)-(Z)-?-Santalol and (–)-(Z)-?-Santalol

“…Sp) gives the highly appreciated essential oil in typically 5-7% yield. [10] The impending lack of supply of East Indian Sandalwood oil was the primary reason behind the plantation of 100 hectares of irrigated Santalum album in the Ord River region of north-western Australia in 1999. [11] Such plantations have been touted as a potential solution to the ever-increasing demand for high quality East Indian Sandalwood oil.…”

“…[22] In addition, the control of the orientation of the sidechain is essential as epi-(Z)-β-Santalol (7) has been shown to be very weak to odourless (Scheme 2). [10] As many well renowned synthetic chemists have tackled both (Z)-α-Santalol (2) and (Z)-β-Santalol (4) it is nonetheless useful to review the various approaches to the (Z)-α-Santalol (2) allylic alcohol sidechain in addition to some aspects of various β-Santalene syntheses.…”

Recent Developments in the Chemistry of Sandalwood Odorants

“…Compound 11a (Fig. 4), discovered by Firmenich researchers, exhibits a powerful, woody note with a clear, very neat sandalwood character [7]. The four-step synthesis of 11a started with the conversion of a-campholenic aldehyde with piperidine into the enamine, which underwent Michael addition with ethyl vinyl ketone to afford the corresponding dione.…”