Tomomi Kawasaki

First Total Synthesis of Hinckdentine A

We have accomplished the first total synthesis of (+/-)-hinckdentine A (1). The key steps are m-CPBA oxidation of 2-arylindole followed by acid-mediated Mannich-type C-C bond formation of 2-hydroxyindolin-3-one, seven-membered ring closure, and regioselective tribromination.

Enantioselective total synthesis of (−)-flustramines A, B and (−)-flustramides A, B via domino olefination/isomerization/Claisen rearrangement sequence

The concise total synthesis of marine alkaloids, (-)-flustramines A and B, and (-)-flustramides A and B has been achieved through the domino olefination/isomerization/Claisen rearrangement (OIC) for highly enantioselective construction of the asymmetric quaternary carbon center and the chemoselective reduction-cyclization (RC) for pyrrolidine formation as key steps.

A short route to “reverse-prenylated” pyrrolo[2,3-b]indolesvia tandem olefination and claisen rearrangement of 2-(3,3-dimethylallyloxy)indol-3-ones: First total synthesis of flustramine C

Abstract The Wittig or Horner-Emmons reaction of 1-acetyl-2-(3,3-dimethylallyloxy)indol-3-ones proceeded via tandem olefination, isomerization, Claisen rearrangement, and deacetylation to give 3-cyanomethyl-3-(1,1-dimethylallyl)indol-2-ones in good yields, which were reduced with Red-Al ® to afford pyrrolo[2,3- b ]indoles having the 1,1-dimethylallyl group at the 3a-position. The first total synthesis of the marine alkaloid flustramine C was also described.

Total synthesis of (+/-)-flustramines A and C, (+/-)-flustramide A, and (-)- and (+)-debromoflustramines A.

Here we describe the efficient total synthesis of the three title hexahydropyrrolo[2,3-b]indole alkaloids and debromo derivative from readily available indolin-3-ones using key domino reactions, olefination-isomerization-Claisen rearrangement (OIC), and reductive cyclization (RC). (+/-)-Flustramine C (5) was synthesized in five steps from 6-bromoindolin-3-one 9 via a key intermediate 13a. (+/-)-Flustramine A (1) has been obtained by reduction of flustramide A (6), which has been prepared in five steps from 13a. (+/-)-Debromoflustramine A (19) was provided in a similar manner from 13b. The (-)- and (+)-enantiomers of 19 were synthesized through optical resolution of (+/-)-carboxylic acid 17b using (R)-4-phenyloxazolidin-2-one.

Total syntheses of (-)-fructigenine A and (-)-5-N-acetylardeemin.

The first total synthesis of (-)-fructigenine A and a novel approach to (-)-5-N-acetylardeemin through a common imine intermediate (+)-3 are described. The key steps include highly enantioselective preparation of (+)-3 via domino olefination/isomerization/Claisen rearrangement (OIC) of 5, reductive cyclization (RC), and regioselective oxidation of (-)-4 and a novel assembly of the pyrazino ring of these alkaloids via Ugi three-component reaction/cyclization of (+)-3 with the corresponding amino acid and isonitrile.

Enantioselective total synthesis of (−)-pseudophrynaminol through tandem olefination, isomerization and asymmetric Claisen rearrangement

A new and efficient total synthesis of (−)-pseudophrynaminol, the pyrrolo[2,3-b]indole alkaloid bearing the allylic moiety at the 3a-position, has been achieved by a sequence involving 3-allylindol-2-one 8 as a key intermediate. The enantioselective construction of the quaternary carbon in 8 was performed through a tandem cascade reaction of 2-allyloxyindolin-3-one 4, olefination, isomerization, and asymmetric Claisen rearrangement.

Syntheses of bis(indolyl)-piperazine alkaloids, dragmacidin B and C, and dihydrohamacanthin A

The syntheses of trans- and cis-isomers of dragmacidin C and 3,4-dihydrohamacanthin A, and dragmacidin B have been accomplished by condensation of two indolylglycines followed by cyclization and reduction. The relative stereochemistry of dragmacidin C was confirmed to be cis, which is distinct from that of other dragmacidins.

Asymmetric Total Synthesis of (−)-Leuconoxine via Chiral Phosphoric Acid Catalyzed Desymmetrization of a Prochiral Diester

The asymmetric total synthesis of (-)-leuconoxine has been achieved. The desymmetrization of a prochiral diester using a chiral phosphoric acid catalyst produced a highly enantioenriched lactam with excellent yield. The ring construction featuring an intramolecular N-acyliminium cyclization and the one-step pyrrolidone formation using Bestmanns ylide was successfully accomplished.

Thionium-Based One-Pot Construction of Homo-/Heterodimeric Pyrroloindoline from Tryptamine

We report a one-pot procedure for forming a dimeric pyrroloindoline framework with a thionium reagent. The cyclization of tryptamine with DMSO and Tf(2)O, followed by substitution with indole derivatives, produced racemic 3a-indolylpyrroloindolines. The method enables rapid access to heterodimeric pyrroloindolines as well as to homodimeric pyrroloindolines.

An Efficient Synthetic Method for 2-Methoxy-L,2-dihydro-3H-indol-3-ones

Abstract An efficient method for synthesis of 2-methoxy-l,2-dihydro-3H-indol-3-ones using two successive oxidations of indoles is described.