Temperature- and Reagent-Controlled Complementary Syn- and Anti-Selective Enolboration-Aldolization of Substituted Phenylacetates.

In contrast to methyl phenylacetates, methyl arylacetates do not provide syn-aldols in the dicyclohexylboron triflate/triethylamine (Chx2BOTf/Et3N)-mediated enolboration-aldolization reaction. However, a combination of a less bulky boron reagent (dibutylboron triflate, n-Bu2BOTf), a bulky amine (i-Pr2NEt), and ambient temperature is required to obtain syn-aldols from methyl arylacetates. The corresponding anti-aldol products have been synthesized by the enolboration-aldolization of methyl arylacetates in the presence of Chx2BOTf/Et3N at a lower temperature. We report the first example of a complementary syn- and anti-selective enolboration-aldolization of arylacetates.

Synthesis and evaluation of duocarmycin SA analogs incorporating the methyl 1,2,8,8a-tetrahydrocyclopropa[c]imidazolo[4,5-e]indol-4-one-6-carboxylate (CImI) alkylation subunit.

The design, synthesis, and evaluation of methyl 1,2,8,8a-tetrahydrocyclopropa[c]imidazolo[4,5-e]indol-4-one-6-carboxylate (CImI) derivatives are detailed representing analogs of duocarmycin SA and yatakemycin containing an imidazole replacement for the fused pyrrole found in the DNA alkylation subunit.

Reprogramming natural proteins using unnatural amino acids.

Unnatural amino acids have gained significant attention in protein engineering and drug discovery as they allow the evolution of proteins with enhanced stability and activity. The incorporation of unnatural amino acids into proteins offers a rational approach to engineer enzymes for designing efficient biocatalysts that exhibit versatile physicochemical properties and biological functions. This review highlights the biological and synthetic routes of unnatural amino acids to yield a modified protein with altered functionality and their incorporation methods. Unnatural amino acids offer a wide array of applications such as antibody-drug conjugates, probes for change in protein conformation and structure-activity relationships, peptide-based imaging, antimicrobial activities, etc. Besides their emerging applications in fundamental and applied science, systemic research is necessary to explore unnatural amino acids with novel side chains that can address the limitations of natural amino acids.

Total Synthesis of Meayamycin and O-Acyl Analogues.

A short, scalable total synthesis of meayamycin is described by an approach that entails a longest linear sequence of 12 steps (22 steps overall) from commercially available chiral pool materials (ethyl l-lactate, BocNH-Thr-OH, and d-ribose) and introduces the most straightforward preparation of the right-hand subunit detailed to date. The use of the approach in the divergent synthesis of a representative series of O-acyl analogues is exemplified.

Enantioselective synthesis of anti- and syn-ß-hydroxy-α-phenyl carboxylates via boron-mediated asymmetric aldol reaction.

A reagent-controlled, diastereo- and enantioselective synthesis of anti- and syn-ß-hydroxy-α-phenyl carboxylates has been achieved by the proper choice of solvent, temperature, alkoxy group, and amine for the diisopinocampheylboron-mediated asymmetric enolization-aldolization of phenylacetates. The pure diastereomers can be readily separated by column chromatography.

Solvent- or temperature-controlled diastereoselective aldol reaction of methyl phenylacetate.

Unlike the enolboration-aldolization of methyl propanoate, the choice of either the solvent or temperature determines the diastereoselectivity during the enolboration-aldolization of methyl phenylacetate. In CH(2)Cl(2), the reaction favors the anti-pathway at -78 °C and the syn-pathway at rt. Conversely, the reaction produces the anti-isomer up to rt and the syn-isomer at refluxing temperatures in nonpolar solvents.