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. 2010 Jul 2;75(13):4356-64.
doi: 10.1021/jo100707d.

Asymmetric synthesis of D-ribo-phytosphingosine from 1-tetradecyne and (4-methoxyphenoxy)acetaldehyde

Zheng Liu  1 , Hoe-Sup Byun, Robert Bittman
Affiliations

Asymmetric synthesis of D-ribo-phytosphingosine from 1-tetradecyne and (4-methoxyphenoxy)acetaldehyde

Zheng Liu et al. J Org Chem. .

Abstract

An asymmetric synthesis of d-ribo-phytosphingosine (1) was achieved by utilizing the ProPhenol (12)-catalyzed alkynylation of unsaturated aldehyde 8 to afford allylic propargylic alcohol (S)-6 followed by asymmetric epoxidation and opening of propargylic epoxy alcohol anti-5 with NaN(3)/NH(4)Cl. Deprotection and reduction of the resulting acyclic azide 3 then gave 1. Alkyne-azide 3 was subjected to an intramolecular click reaction, generating a bicyclic triazole, which was found to have unexpected vicinal coupling constants. Application of the advanced Mosher method verified the configurations of the three contiguous stereogenic centers of 1. An alkynyl azide analogue of 1, which may be useful as a glycosyl acceptor in the synthesis of alpha-galactosylceramide derivatives, was also readily prepared by this route.

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Figures

Figure 1
Figure 1
Partial 1H-NMR spectra of 15 (top) and ent-15/15' (ratio 1:1.2, bottom).
Figure 2
Figure 2
Absolute stereochemistry determination of 13 via the advanced Mosher method.
Figure 3
Figure 3
Absolute stereochemistry determination of 20 by the advanced Mosher method.
Scheme 1
Scheme 1
Retrosynthetic Plan
Scheme 2
Scheme 2
Synthesis of Allylic Propargylic Alcohols (S)-6 and (R)-6
Scheme 3
Scheme 3
Synthesis of Epoxy Alcohols anti-5 and syn-5
Scheme 4
Scheme 4
Opening of anti-5 and Unexpected Coupling Constants in Bicyclic Triazole Derivative 15
Scheme 5
Scheme 5
Conversion of anti-5 to (S)- and (R)-18
Scheme 6
Scheme 6
Conversion of Azido Diol 3 to (S)- and (R)-MTPA Amide 21
Scheme 7
Scheme 7
Completion of the Syntheses of 1 and 4 from 3 and 19, Respectively
Chart 1
Chart 1
Structures of d-ribo-phytosphingosine and α-galactosylceramide (KRN7000).
Chart 2
Chart 2
Reported coupling constants in similar bicyclic systems.
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