Aldol reaction phytosphingosine

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... 

After extensive optimization of the reaction conditions regarding yield as well as diastereo- and enantioselectivity, we were able to obtain the aldol product 26 with 60% yield and excellent diastereo- and enantiomeric excesses (>99% de, 95% ee). Thus, the simple (S)-proline-catalyzed aldol reaction of 4 with pentadecanal directly delivered gram-amounts of the selectively acetonide protected ketotriol precursor 26 of the core unit of phytosphingosines in excellent stereoisomeric purity (Scheme 7). 

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... 

Kumar I, Rode CV (2007) L-Proline Catalyzed Direct Diastereoselective Aldol Reactions Towards the Synthesis of Lyxo-(2S,3S,45)-phytosphingosine. Tetrahedron Asymmetry 18 1975... 

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