Shinichiro Fuse

The development of highly efficient amide bond forming methods which are devoid of side reactions, including epimerization, is important, and such a method is described herein and is based on the concept of rapid and strong activation of carboxylic acids. Various carboxylic acids are rapidly (0.5 s) converted into highly active species, derived from the inexpensive and less-toxic solid triphosgene, and then rapidly (4.3 s) reacted with various amines to afford the desired peptides in high yields

Feglymycin is a naturally occurring, anti-HIV and antimicrobial 13-mer peptide that includes highly racemizable 3,5-dihydroxyphenylglycines (Dpgs). Here we describe the total synthesis of feglymycin based on a linear/convergent hybrid approach. Our originally developed micro-flow amide bond formation enabled highly racemizable peptide chain elongation based on a linear approach that was previously considered impossible. Our developed approach will enable the practical preparation of biologically

A highly efficient, two-stage, continuous-flow synthesis of vitamin D(3) from provitamin D(3) was achieved. The developed method afforded the desired product in high yield (HPLC-UV: 60%, isolated: 32%) and required neither intermediate purification nor high-dilution conditions.

Continuous in situ generation of phosgene and its use in acid chloride formation in a microflow system were demonstrated. The acid chloride was subsequently coupled with an amine in high yield without severe epimerization.

Polymerization of N-carboxy anhydrides (NCAs) is the primary process used to prepare polypeptides. The synthesis of various pure NCAs is key to the efficient synthesis of polypeptides. The only practical method that can be used to synthesize NCAs requires harsh acidic conditions that make acid-labile substrates unusable and results in an undesired ring opening of NCAs. Basic-to-acidic flash switching and subsequent flash dilution technology in a microflow reactor was used to demonstrate the synt

A direct functionalization of unsubstituted isoxazole (1) was achieved by generation of 4-isoxazolyl anion species (3). An efficient 4-iodination of isoxazole and halogen-metal exchange reaction using a turbo Grignard reagent (iPrMgCl⋅ LiCl) were essential for the generation of 3, which reacted with various electrophiles to give 4-functionalized isoxazoles in good to high yields. Isoxazolyl boronate, boronic acid, and stannane were also synthesized as useful building blocks from 1. The current m

Peptide drugs have garnered much attention in recent years. However, conventional peptide synthesis requires an excess amount of expensive reagents of low atom economy, and the large amount of waste produced by these reagents complicates the purification of desired peptides. Solid-phase approaches simplify the purification of these peptides, but these require expensive solid-phase, excess amounts of reagents, substrates, and solvents. This makes it important to develop high-yielding, cost-effect

The creation of organic dyes with excellent high power conversion efficiency (PCE) is important for the further improvement of dye-sensitized solar cells. We wish to describe the rapid synthesis of a 112-membered donor-π-acceptor dye library by a one-pot procedure, evaluation of PCEs, and elucidation of structure-property relationships. No obvious correlations between ε, and the η were observed, whereas the HOMO and LUMO levels of the dyes were critical for η. The dyes with a more positive E(HOM

An efficient, two-stage, continuous-flow synthesis of 1α,25-(OH)(2)-vitamin D(3) (activated vitamin D(3)) and its analogues was achieved. The developed method afforded the desired products in satisfactory yields using a high-intensity and economical light source, i.e., a high-pressure mercury lamp. In addition, our method required neither intermediate purification nor high-dilution conditions.

The development of a robust amide-bond formation remains a critical aspect of N-methylated peptide synthesis. In this study, we synthesized a variety of dipeptides in high yields, without severe racemization, from equivalent amounts of amino acids. Highly reactive N-methylimidazolium cation species were generated in situ to accelerate the amidation. The key to success was the addition of a strong Brønsted acid. The developed amidation enabled the synthesis of a bulky peptide with a higher yield

Conventional peptide synthesis requires a deprotection step after each amidation step, which decreases synthetic efficiency. Therefore, peptide synthesis using unprotected amino acids is considered an ideal approach. Here, we report peptide chain elongation using unprotected amino acids via a mixed carbonic anhydride. Micro-flow technology enabled rapid mixing of an organic layer containing a protected amino acid or dipeptide and an aqueous layer containing an unprotected amino acid or dipeptide

The total synthesis of a natural product HDAC inhibitor, spiruchostatin B, was successfully achieved. A 5-step synthesis that included an asymmetric aldol reaction was carried out in an automated synthesizer to provide an (E)-(S)-3-hydroxy-7-thio-4-heptenoic acid segment that is the crucial structure of cysteine-containing, depsipeptidic natural products such as spiruchostatins, FK228, FR901375, and largazole for their inhibitory activity against HDACs.

Abstract Bayesian optimization (BO) is regarded as an efficient approach that can identify optimal conditions using a restricted number of experiments. Despite demonstrated potential of BO, applications of BO‐based approaches in synthetic organic chemistry remain limited. Herein, we achieved the first rapid and mild (5.1 s, 20 °C) one‐flow synthesis of unsymmetrical sulfamides from inexpensive sulfuryl chloride. Undesired reactions were successfully suppressed and the risk in handling sulfuryl c

Abstract The development of highly efficient amide bond forming methods which are devoid of side reactions, including epimerization, is important, and such a method is described herein and is based on the concept of rapid and strong activation of carboxylic acids. Various carboxylic acids are rapidly (0.5 s) converted into highly active species, derived from the inexpensive and less‐toxic solid triphosgene, and then rapidly (4.3 s) reacted with various amines to afford the desired peptides in hi