Mitsunobu reaction nitrogen groups

Addition of the lithium acetylide of tetrahydropyranyl-protected but-3-yn-l-ol 156 provided the racemic alcohol 157 (Scheme 34). The nitrogen was introduced through a Mitsunobu reaction, followed by oxidation of the primary alcohol to the carboxylic acid and a change of the phthaloyl protecting group to Boc protection. The latter reaction was necessary because hydrazinolysis of the C-terminal amide analogue of 159 did result in deeply red-colored mixtures, indicating that phthaloyl removal by this method should occur prior to peptide synthesis. 131 ... 

Alkylated prolines can be incorporated into synthetic peptides as mimics for the p-turn found in the conformation of folded proteins. One such compound9 combines a spirocyclic proline derivative 77 with tyrosine. The allyl group in 74 is oxidatively cleaved to give 75 and eventually coupled to the nitrogen atom of the amide in 76 by a Mitsunobu reaction. 

N-Sulfonylcarbamates. Prepared by reaction of methanesulfonamide with t-butylchloroformate (Et,N-DMAP as base). As a nucleophile in the Mitsunobu reaction, various alkyl groups can be attached to the nitrogen atom. 

Other approaches from acyclic precursors are through the formation of the 1,4- or 3,4-bonds of the laetam. The former can be achieved by nucleophilic attack of the amide nitrogen on an activated carbon atom. A suitable P-substituent in the amide is a hydroxyl group and cyclisation can be accomplished by the action of carbon tetrachloride-triphenylphosphine in the presence of a base <00T5719>, by use of the Mitsunobu reaction conditions <01TL1247>, or by formation of the mesylate and subsequent treatment with base to activate the amide. Investigation of this last process with amide 62 has shown that both 63 and 64 are formed in the ratio of 1 50, respectively <00TL8539>. 

The oxorhenium(V) complex 80 has been prepared from 2, 3 -diamino-2, 3 -dideoxyadenosine, and exists as a 2 1 mixture of syn- and an/i-isomers. Both were inhibitors of purine-specific ribonuclease, with the 57/i-isomer being more effective. " The same group has described a route to 3, 5 -diamino-3, 5 -dideoxy-adenosine (82) from the /> xo-epoxide 81 (Vol. 25, p. 251-2), as outlined in Scheme 10. The Mitsunobu inversion using benzyl alcohol as nucleophile is noteworthy, and proved superior to other strategies. An oxorhenium(V) complex was also formed from 82." Thymidine can be converted into the anhydronucleo-side 83 by two successive Mitsunobu reactions, and 83 was converted into the aminoderivative 84 of AZT, and some phosphoramidates were produced from 84." Some 5 -deoxy-5 -sulfonylamido derivatives of AZT have also been produced by successive displacements at 0-5 and 0-3 by nitrogen nucleophiles." ... 

This was shown to be possible in substitution reactions of aminoalcohols where the type of nitrogen-protecting group determines the outcome of a Mitsunobu reaction [142]. 

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