Phytosphingosines derivatives

Kobayashi s group9 isolated novel phytosphingosine-derived azetidine alkaloids, penaresidines 6, with potent actomyosin ATPase activating activity from the sponge Penares sp. 

Glycosphingolipids 1 and 11 could be readily purified from pooled reactions fiom kinetic analyses, and indeed 10-20 mg quantities were obtained in that way. To fiirdier demonstrate die synthetic utility of the evolved D314Y mutant, the syndiesis of phytosphingosine-derived... 

Ij o-Gm3 (13) was carried out on a 10 mg scale. A 1.5 1 molar ratio of GmsOSF (14) 6 was incubated in 25 mM NaOAc, pH 5,10% (v/v) 1,2-dimethoxyethane with a 20 pM final concentration of the D314Y mutant The reaction showed complete consumption of 6, and gave a 54% purified yield, thus demonstrating to our knowledge the first synthetic access to phytosphingosine-derived glycosphingolipids. 

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... 

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... 

Sphingolipids, important membrane components of animals and plants, contain a complex long-chain amino alcohol (either sphingosine or phytosphingosine). The core of each sphingolipid is ceramide, a fatty acid amide derivative of the alcohol molecule. Glycolipids are derivatives of ceramide that possess a carbohydrate component. 

In the Table I are listed some sphingosines, dihydrosphingosines, phytosphingosines, and so on, that have been isolated by hydrolysis of sphingolipids of animal or plant origin. Table II lists some derivatives of these compounds that can be obtained from the natural sphingosines by such simple chemical transformations as acylation. 

An alternative versatile starting material is 2,4-Obenzylidene-D-threose 35, which is readily obtained from D-galactose. Retrosynthetic analysis indicates that the 2,4-disubstituted D-threose derivative and carbanions would offer a shorter route to D-ribo-phytosphingosines as well as D-ribo-dehydrophytosphingosines (Scheme 5). 

Kobayashi s group37 developed a new enantioselective synthesis of Cis phytosphingosine using catalytic asymmetric aldol reactions as a key step (Scheme 23). The key catalytic aldol reaction of acrolein with the ketene silyl acetal 148 derived from phenyl a-benzyloxyacetate was carried out by using tin(II) triflate, chiral diamine 149, and tin(II) oxide. The desired aldol product... 

In an interesting application of enolate chemistry associated with silyl derivative 79, electrophilic amination allows convenient access to the synthetic equivalent of 2-deoxy-2-aminotetroses. This methodology has been applied to the stereoselective synthesis of D-ribo- Ci8-phytosphingosine (96) (Scheme 11) [41]. 

Ibata s group extended this methodology to include a-alkoxyaldehydes and developed an elegant asymmetric synthesis of chiral erythro-2-waino polyol derivatives, such as those found in D-ABl 813,1-deoxynorjirimycin 814, sphingo-sine 815, and phytosphingosine 816 (Fig. 1.62). For example, reaction of 806 with... 

Naturally occurring phytosphingosine possesses a 25,35,4/ absolute configuration. As shown in Fig. 1, KRN7000 (2) derived from the natural... 

The common and most abundant long-chain bases in sponge and echinoderm cerebrosides are derived from sphingosine ((2S, 3/ ,4 )-2-amino-4-octadecen-1,3-diol) (3) and the saturated phytosphingosine ((25,35,4/ )-2-amino-octadecan-triol)(4)(Fig.2). 

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