Thioacids reactivity

The data in the tables can generally be interpreted satisfactorily without invoking such orientation effects. This is not to say that they do not exist at all, but simply that they must be relatively small. The major difficulty in identifying any small effect is the elimination of all other possibilities. Storm and Koshland (1972ab) have made the best attempt to do this in their discussion of the relative rates of lactonization of the series of hydroxy and thioacids B.2.1-9 and C.2.1-5, but these rates were found to parallel the equilibrium constants for the lactonization, and it seems probable that the dominant effect controlling reactivity in these systems—and not corrected for—is the relief of ground-state strain discussed above. 

As an extension of this chemistry, the [3+2] cycloaddition reaction of new atropisomeric 4-dialkylamino-5-chloro-l,2-dithiole-3-thiones 130 and DMAD or its diethyl analogue has been utilized to give thioacid chlorides 131 (Scheme 13) <20030L929>. These have been converted into thioamides 132 with 2 equiv of pyrrolidine (or morpholine) by substitution of the 5-chloro substituent and phthalimide ring opening. Similar reactivity toward 1 or 2 equiv of pyrrolidine was noted for 130, which was obtained according to the general method described. 

Examples of efficient ligation methods for creating artifically linked proteins or peptides include formation of thioesters by reaction of a thioacid and a bromoacetamide [119], formation of pseudoproline residues from an aldehyde and Cys or Thr [122,124], formation of an oxime from an amino-oxy function and an aldehyde or ketone [120,121], and formation of a hydrazone from a hydrazide and an aldehyde [121,125,126]. Several of the preceding methods may be used in series because of different reactivities. 

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