Lactonization methods

Natural product total syntheses are particularly valuable when they are attended by the development of general utility methods of synthesis. In some instances, the successful completion of a natural product total synthesis requires the development and application of a new synthetic method. The total synthesis of erythronolide B by Corey et al. is one of these instances. The double activation macro-lactonization method was a fruitful innovation that was introduced in response to the challenge presented by the macrocyclic structures of the erythromycins. Several other methods to achieve the same objective, and numerous applications followed. 

Vitamin Bg and related compoimds (Figure 10.2) were quantitatively separated by preparative TLC on silica gel H. After elution, the pyridoxic acid lactone method was employed for fluorimetric determination of the concentration of the vitamin forms involved [8]. Table 10.2 shows Revalues obtained for various forms of vitamin Bg, using several solvent systems. The solvent selected, ethyl acetate/pyridine/water (2 1 2, v/v), gave excellent separation of pyridoxamine, pyridoxic acid, and pyri-doxine together with pyridoxal. 

The above discussion is a summary of the lactonization methods known at present newer methods continue to be explored. The selection of a method for an individual case depends to a large extent on the structure and functionalities of the substrate. Detailed comments in this respect are reserved until more information has accumulated. 

Whistler, R L, BeMiller, J N, a -D-Glucosaccharino-1,4-lactone, Methods Carbohydr. Chem., 2, 484-485, 1963. 

The value of naphtho[2,l-()]coumarins in the atroposelective synthesis of axially chiral hiaryls, the so-called lactone method, has been discussed with emphasis on an approach to chiral phosphineamines <04T4349, 04T6335>. 

Corey et al. [36] developed an efficient and mild lactonization method using 2-pyridinethiol ester. Slow addition of 2-pyridinethiol esters, prepared from to-hydroxy acids by reaction with 2,2 -dipyridyl disulfide and Ph3p or 2-fhiopyridyl chloroformate and EljN, to refluxing xylene under dilution conditions yielded... 

Coupling yields by the diisothiocyanate method are generally good, and this procedure ranks with the homoserine lactone method in terms of reliability. The glass supports are usually better for peptides consisting of... 

The C14-C20 segment [83] The route adopted for the chiral synthesis of the C14-C20 segment followed their replicating lactone method [89, 90] starting from the same lactone 102 (Scheme 14). A standard five-step transformation of 102 provided the epoxide 109 on which a two-carbon extension sequence [89, 90] furnished the replicated butenolide 110. Conjugate addition of the bulky lithium m s(methylthio)methane followed by an enolate hydroxylation... 

Corey EJ, Nicolaou KC (1974) An Efficient and Mild Lactonization Method for the Synthesis of Macrolides. J Am Chem Soc 96 5614... 

Corey-Nicolaou S-Pyridyl Ester Lactonization Method... 

Mukaiyama developed l-alkyl-2-halopyridinium salts, which are useful reagents for the preparation of carboxylic esters and lactones in the presence of tertiary amines [22]. After generation of activated onium salts from the corresponding co-hydroxycarboxylic acids, spontaneous lactonization smoothly proceeds to produce various macrolactones. Bartlett first used this lactonization method for the... 

Rao synthesized the unnatural (-b)-cephalosporolide D (ent-1) using the Yamaguchi lactonization method [58]. Cyclization of the seco-acid 41 activated by 2,4,6-trichlorobenzoyl chloride and a catalytic amount of DMAP formed eight-membered lactone 42 in 68% yield (Scheme 5.13). 

The P-Lactone Method. Dimethylketene has been prepared in 50% yield by pyrolysis of a-carbomethoxy-a,/3-dimethyl-/3-butyrolactone. The lactone was prepared from acetone and methylmalonic acid. The... 

The Shanzer lactonization method produces a lower overall yield of macrolides, but an increased ratio of the higher homologs. ... 

---