Selective Acylations of Multifunctional Nucleophiles, Including Carbohydrates and Nucleosides, with Intermediates Generated by Wolff Rearrangement of Amino Acid Derived Diazo Ketones: Preparation of β‐Amino Acid Derivatives

Abstract

The diazo ketones derived from Z‐ and Boc‐protected alanine, valine, and alanyl‐alanine (1–5) were decomposed by catalytic amounts of silver benzoate/Et3N in the presence of polyfunctional nucleophiles such as 3‐methyl‐1,3‐butanediol, 2‐aminoethanol, carbohydrates (xylofuranose and sucrose) and nucleosides (thymidine, adenosine derivatives). In many cases, products of β‐amino acylations are formed (6–14, 15b, 17–19, 21, 23, 24) with surprising functional group selectivities. The scope and limitations of the method are described.

Electrophilic S‐Trifluoromethylation of Cysteine Side Chains in α‐ and β‐Peptides: Isolation of Trifluoro‐methylated Sandostatin® (Octreotide) Derivatives

“…The importance of trifluoromethylations in medicinal chemistry and possible applications of the method (spin-labelling, imaging, PET) are discussed. [7]. In continuation of this tradition, we have now investigated the conversion of CH 2 ÀSÀH groups of cysteine side chains in peptides to CH 2 ÀSÀCF 3 groups, by using a method [8] [9] that has been recently introduced by another group of co-authors of the present article 5 ).…”

Preparation of Enantiopure β-Amino Acids by Homologation of α-Amino Acids

“…Not only water or alcohols have been used as nucleophiles in the formation of homologated amino acid derivatives but also amino esters, 13 peptides, 13 sugar, 21,22 nucleotide, 22 and nucleoside derivates (Scheme 3.4). 22 Rearrangement in the presence of N,O-dimethylhydroxylamine proved to be a very convenient method for the preparation of the respective Weinreb hydroxamic acids, which can be further reduced to the corresponding b-amino aldehydes.…”

“…22 Rearrangement in the presence of N,O-dimethylhydroxylamine proved to be a very convenient method for the preparation of the respective Weinreb hydroxamic acids, which can be further reduced to the corresponding b-amino aldehydes. 23 Though ketenes are very reactive intermediates and thus might be expected to be nonselective acylating agents, selectivities are astonishingly high in competitive trapping experiments.…”

“…23 Though ketenes are very reactive intermediates and thus might be expected to be nonselective acylating agents, selectivities are astonishingly high in competitive trapping experiments. 22,24 Using 2-methyl-butan-2,4-diol, a preferential acylation of the primary hydroxy function is observed with a selectivity of 19 : 1 (Scheme 3.5). With 2-aminoethanol an exclusive formation of the respective amide is achieved.…”

Novel and efficient regioselective enzymatic approach to 3′-, 5′- and 3′,5′-di-O-crotonyl 2′-deoxynucleoside derivatives

“…Moreover, the presence of this moiety on nucleosides would afford excellent starting compounds for the synthesis of, e.g., β-amino acid analogues of potential interest. 11 Nevertheless, the synthesis of O-crotonyl derivatives is not trivial since it is known that in the usual conditions to obtain them (base-catalyzed process with crotonyl chloride), mixtures of desired compounds and β,γ-unsaturated analogues are provided due to the deconjugation of the double bond. This fact, firstly described in 1966 by Ozeki and Kusaka, 12 depends on several factors such •as the alcohol, the solvent, the amine, and the temperature.…”