- An improved two-step synthetic route to primary allylic alcohols from aldehydes
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An improved two-step synthetic route to allylic alcohols from aldehydes has been developed. A modification of the HWE reaction in H2O-2-PrOH (1 : 1) and a convenient protocol to prepare AlH3 in THF from LiAlH 4 and n-BuBr are the key factors in the improvement.
- Liu, Zheng,Gong, Yaqiong,Byun, Hoe-Sup,Bittman, Robert
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experimental part
p. 470 - 475
(2010/06/14)
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- Asymmetric synthesis of d - Ribo -phytosphingosine from 1-tetradecyne and (4-Methoxyphenoxy)acetaldehyde
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(Figure presented) 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 NaN3/NH4Cl. 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 α-galactosylceramide derivatives, was also readily prepared by this route.
- Liu, Zheng,Byun, Hoe-Sup,Bittman, Robert
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supporting information; experimental part
p. 4356 - 4364
(2010/10/02)
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- Enantioselective synthesis of a novel trans double bond ceramide analogue via catalytic asymmetric dihydroxylation of an enyne. The role of the trans double bond of ceramide in the fusion of Semliki Forest virus with target membranes
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Intensive interest is currently focused on the role of ceramide (1), a key lipid molecule that functions as a second messenger. The first asymmetric synthesis of a D-erythro-ceramide analogue that contains a C(5)C(6) trans double bond (3), together with its biological evaluation in a viral-liposome fusion system, is described. Sharpless asymmetric dihydroxylation of 4'- methoxyphenyl trans-5-octadecyn-2-enyl ether (enyne 8a), prepared by the coupling reaction of 1-[(E)-(4'-bromo-2'-butenyl)oxy]-4-methoxybenzene (7) with lithium tetradecyne, generated yne-diol 9 in 96% yield with the desired stereochemistry at the C(2) and C(3) positions and high enantiomeric purity (95% enantiomeric excess). Birch reduction (Li/EtNH2) of yne-diol 9 furnished (2R,3R,5E)octadecene-1,2,3-triol (10) stereospecifically. The latter was converted to 2-azido derivative 13 in three steps (via a 2-O- triflate-1,3-O-benzylidene intermediate) and 55% overall yield. Reduction of azide 13 and in situ N-acylation with p-nitrophenyl cis-hexadec-4-enoate provided D-erythro-Δ5-trans-ceramide (3) in 91% yield. The role of the trans double bond of ceramide in mediating fusion of an alphavirus (Semliki Forest virus) was assessed in a liposomal model system, using target phospholipid/cholesterol vesicles containing either D-erythroceramide 1 or 3. The kinetics of virus fusion, as monitored by a change in pyrene excimer fluorescence over a period of 60 s, showed that Δ5-trans-ceramide 3 was completely inactive, indicating that there is an absolute requirement for the trans double bond to be located between C(4) and C(5). These data indicate that the molecular determinants on the viral envelope glycoprotein are highly specific for recognition of the unsaturated site in the ceramide molecule.
- He, LinLi,Byun, Hoe-Sup,Smit, Jolanda,Wilschut, Jan,Bittman, Robert
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p. 3897 - 3903
(2007/10/03)
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