Phytosphingosines

This method has been applied in the enantioselective synthesis of d-erythro-sphingosine and phytosphingosine. Sphingosine became an important substance for studying signal transduction since the discovery of protein kinase C inhibition by this compound.48 Many efforts have been made to synthesize sphingosine and its derivatives.49 Kobayashi et al. reported another route to this type of compound in which a Lewis acid-catalyzed asymmetric aldol reaction was a key step. 

In the synthesis of D-eryt/zro-sphingosine (78 without BOC protection), the key step is the asymmetric aldol reaction of trimethylsilylpropynal 75 with ke-tene silyl acetal 76 derived from a-benzyloxy acetate. The reaction was carried out with 20 mol% of tin(II) triflate chiral diamine and tin(II) oxide. Slow addition of substrates to the catalyst in propionitrile furnishes the desired aldol adduct 77 with high diastereo- and enantioselectivity (syn/anti = 97 3, 91% ee for syn). In the synthesis of protected phytosphingosine (80, OH and NH2 protected as OAc and NHAc, respectively), the asymmetric aldol reaction is again employed as the key step. As depicted in Scheme 3-27, the reaction between acrolein and ketene silyl aectal 76 proceeds smoothly, affording the desired product 80 with 96% diastereoselectivity [syn/anti = 98 2) and 96% ee for syn (Scheme 3-27).50... 

Murakami and Taguchi utilized a diastereoselective Grignard addition to a substituted-chiral oxazoline aldehyde 524 (Scheme 8.170) in an improved stereoselective synthesis of D-n7 o-phytosphingosine. The good stereoselectivity observed for 525 can be rationalized by a Felkin-Ahn transition state model although a chelation control mechanism could not be mled out. 

The composition of the ceramide moiety of these glycolipids is quite similar. Among the fatty acids, normal and a-hydroxy acids were detected the latter accounted for 10% of the mixture of acids. In the monosialogly-colipid, the major components of the normal acids are C14 0 and C16 0 acids, and of the a-hydroxy acids, the C15 0, C17 0, and C24 0 a-hydroxy acids. The sphingosine bases are phytosphingosines the preponderant ones are C18 and C19 phytosphingosines.140,293... 

Scheme 31 Access to phytosphingosines through P-lactam ring opening by lithiated sulfones...

This effect was used to prepare the tetrahydropyranyl ether (3) of racemic phytosphingosine,2 a base characteristic of plant sphingolipids (equation II). 

Since the synthesis of glycolipids involves the synthesis of both the lipid and the oligosaccharide portions, we shall also discuss that part of the recorded lipid synthetic work which has involved the use of carbohydrates. In fact, some of the first-recorded applications of carbohydrate molecules as chiral templates are to be found in the lipid field particularly with the use of 1,2 5,6-di-O-isopropylidene-D-mannitol [33] as a precursor of chiral glycerol derivatives for the synthesis of phospholipids and glycolipids based on glycerol and with the use of glucosamine derivatives for the synthesis of phytosphingosines [34] and since this area has not previously been reviewed, it will be treated with a more historical perspective. 

A further synthesis of phytosphingosine (11) was achieved [37] from D-galactose via 3,4,6-tri-O-benzyl-D-galactose. Reduction of the latter and subsequent acetonation gave the galactitol derivative (7), and this on mesylation and reaction with potassium... 

Iwamori, M. Costello, C. and Moser, H.W. Analysis and quantitation of free ceramide containing nonhydroxy and 2-hydroxy fatty acids, and phytosphingosine by high-performance liquid chromatography. J. Lipid Res., 1979, 20, 86. 

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