Lactic acid protected derivatives

Bases N-protected amino acids Tartaric acid and derivatives (dibenzoyl- and di-p-toluyltartaric acids) Mandelic acid and derivatives (O-acetylmandelic acid and O-methylmandelic acid) l,l -Binapthylphosphoric acid Camphorsulfonic acid Deoxycholic acid Cyclic phosphoric acid Others (malic acid, lactic acid and derivatives, Mosher s acid, N-derivatized amino acids, etc.) The same reagents as for acids (brucine, quinine, ephedrine, pseudoephedrine and synthetic chiral bases) [32-35] [36-38] [39-40] [41] [42] [29] [43-45]... 

In addition to the more or less popular methods of depsipeptide synthesis discussed vide supra, there are also a limited number of complementary and effective synthetic procedures that have been described for this purpose. Among these, the well-known method of symmetric anhydrides from N-protected amino acids has to be considered. This method has found successful use in the esterification of hydroxy acids in the presence of some catalyst additives. Initially, the addition of pyridine11091 or 1-hydroxybenzotriazole in pyridine1 101 to a symmetric anhydride was utilized for ester bond formation. As an example, Katakai has prepared a number of didepsipeptides in 85-96% yield by means of a 2-nitrophenylsulfenyl /V-carboxy anhydride with lactic acid derivatives in the presence of pyridine.1 09 ... 

This chapter is organized according to the nature and complexity of lactic acid itself and its derivatives. We begin by discussing the chemistry surrounding lactic acid and its esters. Then lactic acids with the hydroxyl function protected by a variety of removable groups are presented sequentially. A table of physical data associated with all the common protected lactic acid derivatives, discussed throughout this part of the book is presented at the end of the chapter. 

Chiral allylic acetates 426 can be prepared using a similar j5-ketophosphonate (425), also derived from lactic acid. The desired 425 is formed via reaction of lithiated diphenylphos-phonate with 401. Reduction of the ketone gives an intermediate alcohol which, upon treatment with base, forms the ( )-Wittig olefin. Removal of the silyl protecting group followed by acetylation gives the product 426 (> 98% ee) [133]. 

The chemistry associated with trityl-protected lactic acid derivatives is associated mainly with the corresponding lactaldehyde, and is discussed in Section 1.5.8. 

Acetylenic diols, potential building blocks for the synthesis of L-hexoses and L-pentoses, are available with either syn or anti configuration using TBPS-protected L-lactic acid derivatives as the chiral source (Scheme 108). 

Scheme 53 illustrates the final construction of the spiroacetal. Alkylation of the dianion of the lactic acid-derived acetyl butyrolactone (R)-394 with iodide (R)-392 furnishes 395. Hydrolysis of 395 with concomitant decarboxylation furnishes 396 which, upon removal of the THP protecting group under acidic conditions, forms the (2R,5R,7R)-diastereomer 397 in 42.6% overall yield from (R)-392. 

Preparation of an useful synthon, the cyclic carbamate of L-daunosaminal (104), was achieved by sequential catalytic transformations of a key intermediate. Suitably protected propargyl diol 101, which was obtained by diastereoselective addition of allenyl stannate 99 to 0-benzyl (S)-lactyl aldehyde 100, was transformed as depicted in Scheme 18. Cycloisomerization to 3-deoxyglycal 103 was achieved by irradiation in the presence of tungsten hexacarbonyl, and subsequent nitrene insertion was catalyzed by rhodium acetate. Overall yield of the bicyclic daunosaminal (104) derivative from lactic acid derivative amounted to 44% [78]. 

Although most synthetic approaches to L-daunosamine start from carbohydrate precursors, some routes employ chiral synthons derived from other sources. The aldehydes 213 obtained through reaction of cinnamaldehyde with acetaldehyde in the presence of Baker s yeast followed by ozonolysis [157], and 214 obtained from L-tartaric acid [158-160] have been utilised in the synthesis of daunosamine derivatives, and protected daunosamines and acosamines have been synthesised from (synthetic approaches have employed lactic acid as a chiral starting material [162, 163] and the (S)-amine 215 obtained by resolution has been converted to V-benzoyl daunosamine together with its 3-epimer [164]. Wovkulich and Uskokovic have... 

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