Unprotected hydroxyl amino groups

If amino acids with unprotected hydroxyl groups are incorporated, it is better to use carbodiimide activation (such as DIC/HOBt-activation) instead of more reactive procedures to avoid acylation of the hydroxyl-groups. 

A further improvement of the efficacy against resistant strains was reported for the 5"-amino-3, 4, 5 -trideoxy derivatives, the syntheses of which has been published by two different groups (W. K. Woo et al. and H. Saeki et al. W. K. Woo et al. protected the 3, 4 -hydroxyl groups of 135 via a cyclohexylidine group, ace-tylated the unprotected hydroxyl functions and removed the cyclohexylidine groups. The liberated 3, 4 -hydroxyl groups were mesylated. Subsequent iodination and reduction yielded 5 -amino-3, 4, 5"-trideoxybutirosin A 118. 

The N-terminal residue should be incorporated as an IV-Boc derivative, or the N-terminal amino group can be capped by treating the resin with di-t-butyl-dicarbonate (5 eq) in DMF for 30 min. The former method is preferred when the peptide contains residues with unprotected side-chain hydroxyl functionalities. 

Scheme 60). Griesbeck et al. assume that in a non-polar solvent such as benzene the intramolecular electron transfer from the methionic sulfur group is much faster than the abstraction of hydrogen from the hydroxyl group of the unprotected amino acid. C-Hydrogen abstraction leads to 313, whereas previous lactonization of the zwitterionic biradical 311 yields 314. Since the cis-hydroxy acid is not detected it is conceivable that it cyclizes immediately to the lactone 314. Photolysis of the corresponding methyl ester under the same conditions attains improved yields (84% combined) of two diastereomeric tricyclic products in a ratio of 48 52. 

This two-step methylation sequence, involving 2-azanorbornene synthesis and retro Diels-Alder initiated iminium-ion reduction, is applicable to a variety of amino acid derivatives. The protocol is compatible with unprotected phenols and hydroxyl groups. The 2-azanorbornenes derived from the methyl esters of unprotected L-tyrosine and L-serine both undergo the N-... 

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