Oxidation of natural targets by dioxiranes. Part 4: A novel approach to the synthesis of N-hydroxyamino acids using dioxiranes

Oxidation of Peptides by Methyl(trifluoromethyl)dioxirane: The Protecting Group Matters

“…The reaction is assumed to occur without loss of enantiomeric excess. 10 The structure of the compound 2a and of the following oxidation products that are described in this work were unambiguously characterized by the combination of high resolution mass and 1D and 2D NMR techniques. The reaction conditions adopted in the oxidation of dipeptide 2 were used in the oxidation of the other Boc protected peptides bearing alkyl side chains.…”

“…This rationale holds for the observed behavior of dimethyldioxirane in the reaction with Boc-Leu-OMe and Boc-Val-OMe, where it is reported that with Boc-Leu-OMe, the 4,4-dimethyl-4-butanolide derivative was produced, whereas Boc-Val-OMe did not react with DMD. 8 The oxidation products of N-Ac-Leu-Ala-OMe (9) and N-Ac-Ala-Leu-OMe (10) were NAc-Leu(γ-OH)-Ala-OMe (9a) (54% isolated yield) and N-Ac-Ala-2-amino-4,4-dimethyl-4-butanolide (10a) (36% isolated yield), respectively (entries 3-4). The β-CH bond of valine in Ac-Val-Ala-OMe (11) reacted to a lower extent, as in the simpler case 8, N-Ac-Val(β-OH)-Ala-OMe (11a) being produced in 12% yield (entry 5).…”

“…The major product for the oxidation with TFD is the N-hydroxy derivative of Boc-Leu-OMe (57% yield, no loss of enantiomeric excess) along with the N-hydroxy derivative of the butanolide (21% yield). 10 We have extended the study of the reaction of TFD with Boc protected di-and tripeptide esters bearing alkyl side chains. In all the cases analyzed, we observe selective hydroxylation of the terminal nitrogen atom in short reaction times and remarkably mild reaction conditions.…”

Remote C(sp3)–H Oxygenation of Protonated Aliphatic Amines with Potassium Persulfate

“…2b,3 In contrast, it remains much more challenging to selectively functionalize less activated C(sp 3 )–H bonds that are remote from nitrogen. 4,5 The incorporation of various nitrogen protecting groups including carbamates, 6 amides, 7 imides, 2a,8 and sulfonamides 3f,9 has been used to deactivate the α-C–H bonds and enable C(sp 3 )–H functionalization at alternate sites. Similarly, directing groups have been appended to nitrogen to enforce remote C(sp 3 )–H functionalization.…”

Selective Synthesis of Hydroxy Analogues of Valinomycin using Dioxiranes

“…For instance, in the selective hydroxylation of N -protected di- and tripeptides, dioxirane attack at the γ-CH of leucine or at the β-CH of valine residues could be selectively directed at the alkyl side chain using amide-type protecting groups, such as acetyl (Ac), trifluoroacetyl (Tfa) or pivaloyl (Piv). 5a,b …”