Fluorine fluoroamino acids

This chapter deals with fluorinated analogues and derivatives of natural products. We report on examples of fluoro analogues taken from the main families of natural compounds. This chapter is not exhaustive, and mainly focuses on biological applications and medicinal chemistry. Fluoropeptides, fluoroamino acids, and fluor-ocarbohydrates are the topics of Chapters 5 and 6, respectively. 

The low-temperature fluorodehydroxylation technique is a convenient method for the preparation of fluoroamino acids from hydroxyamino acids. The displacement of hydroxy groups by fluorine proceeds with predominant inversion of configuration as exemplified by the fluorination of L-thrconine (3) and L-a//p-threonine (4).40... 

Substituted 2-oxazolidones 165 are useful chiral auxiliaries for diastereoselective functionalization at the a-carbon of their amide carbonyl group. The a-fluoroaldehydes 166 were prepared by a series of reactions electrophilic fluorination of the corresponding oxazolidinone sodium enolates with AMluorobenzenesulfonimine reductive removal of the auxiliary with LiBH4 and Dess-Martin oxidation. The aldehydes are so unstable for isolation that they are converted with (R)-/ -toluenesulfinamide to /7-toluenesul(inimines 167, which are isol-able and satisfactorily enantio-enriched. Chiral sulfinimine-mediated diastereoselective Strecker cyanation with aluminum cyanide provided cyanides 168 in excellent diastereose-lectivity, which were finally derived to 3-fluoroamino acids 169 (see Scheme 9.37) [63]. 

In the synthesis of 3-fluoroamino acid 256 (Scheme 9.55), fluorination of alcohol 251 (R2 = H) with morpho-DAST afforded the desired alcohol only in low yield (10-25%). The same reaction of trimethylsilyl ether 251 (R2 = TMS) improved the yield (50%). The Mitsunobu amination of the secondary hydroxyl group in 254 successfully gives 255 in 89% yield. Starting from 250, several fluorinated a- and P-amino acids 257-259 have been prepared [31]. 

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