Takeshi Oishi

Concise synthesis of α-trisubstituted amines from ketones using N-methoxyamines.

Three-component allylation and cyanation utilizing a ketone and an N-methoxyamine are reported. The high nucleophilicity of the N-methoxyamine and high electrophilicity of the corresponding iminium ion enable the concise synthesis of α-trisubstituted amines in a single step.

Synthesis of paclitaxel. 2. construction of the ABCD ring and formal synthesis

A formal synthesis of the antitumor diterpenoid paclitaxel (Taxol) is described. The ABC ring of paclitaxel, synthesized starting from 1,3-cyclohexanedione and tri-O-acetyl-d-glucal by SmI2-mediated cyclization as the key transformation, was successfully converted to Takahashis tetracyclic oxetane intermediate. A double Chugaev reaction was employed for introduction of the strained bridgehead olefin, and stereoselective formation of the oxetane ring afforded the known synthetic intermediate, completing the formal synthesis of paclitaxel.

Unified Total Synthesis of Stemoamide-Type Alkaloids by Chemoselective Assembly of Five-Membered Building Blocks

A unified total synthesis of stemoamide-type alkaloids is reported. Our synthetic approach features the chemoselective convergent assembly of five-membered building blocks via stemoamide as the common precursor to tetracyclic natural products. The synthesis consists of two successive coupling reactions of the three five-membered building blocks. The first coupling reaction is the vinylogous Michael addition/reduction sequence, which enables the gram-scale synthesis of stemoamide. The second coupling reaction is a chemoselective nucleophilic addition to stemoamide. While the lactone-selective nucleophilic addition to stemoamide affords saxorumamide and isosaxorumamide, the lactam-selective reductive nucleophilic addition leads to the formation of stemonine. Both chemoselective nucleophilic additions enable direct modification of stemoamide, resulting in highly concise and efficient total syntheses of the stemoamide-type alkaloids.

Total Synthesis of Sphingofungin F by Orthoamide-Type Overman Rearrangement of an Unsaturated Ester

The total synthesis of sphingofungin F through the Overman rearrangement of an unsaturated ester, which is known to be an unsuitable substrate under standard conditions due to the competitive aza-Michael reaction, is described. The developed conditions enabled the ester to be compatible with the original Overman rearrangement, providing quick access to α,α-disubstituted amino acids by minimizing extra protecting group manipulations and redox reactions.

Synthesis of Paclitaxel. 1. Synthesis of the ABC Ring of Paclitaxel by SmI2-Mediated Cyclization

A convergent synthesis of the ABC ring of antitumor natural product paclitaxel (Taxol) is described. SmI2-mediated reductive cyclization of an allylic benzoate possessing an aldehyde function, synthesized from tri-O-acetyl-d-glucal and 1,3-cyclohexanedione, smoothly afforded the highly strained 6-8-6 tricarbocyclic structure in 66% yield.

Crystal structure of (±)-(4RS,5RS,7SR)-4-[(1RS,2RS,3RS,6RS)-3-benzo-yloxy-2-(2-hy-droxy-ethyl)-6-meth-oxy-meth-oxy-2-methyl-cyclo-hex-yl]-8,10,10-trimethyl-2-oxo-1,3-dioxa-spiro-[4.5]dec-8-en-7-yl benzoate benzene monosolvate.

In the title compound, the ring conformations of the tricycles are in an envelope, a half-chair and a chair. In the crystal, intermolecular O—H⋯O and C—H⋯O hydrogen bonds and C—H⋯π interactions link the molecules into a three-dimensional architecture.

Stereoselective total synthesis of (+)-myriocin from D-mannose

The stereoselective total synthesis of myriocin 1 from D-mannose is described; the carbon framework with three contiguous chiral centers including a tetra-substituted carbon with nitrogen was effectively constructed using Overman rearrangement as the key reaction.

(2S,3R,4S,5R,6S)-6-Benzyl­oxy­methyl-4-(methoxy­methyloxy)-9-oxo-8-oxa-1-aza­bi­cyclo­[4.3.0]­nonane-2,3,5-triyl tri­acetate

The relative configuration of the title compound, C(23)H(29)NO(11), prepared in a synthetic study on the natural product sphingofungin E, has been determined. The six-membered ring adopts a chair form and the five substituents are all axial.

Crystal structures of (±)-(1SR,5SR,6SR,7SR,10SR,11SR,13RS,14SR)-13-hy­droxy-7-meth­oxy­meth­oxy-11,15,18,18-tetra­methyl-3-oxo-2,4-dioxa­tetra­cyclo­[12.3.1.01,5.06,11]octa­dec-15-en-10-yl benzoate, its 13-epimer and 13-one derivative

In the title three compounds, the ring conformations of tetracycles are similar; each tetracycle adopts essentially planar, chair, half-chair and chair–chair forms. In the crystals, molecules are linked into similar chains by intermolecular hydrogen bonds.

Crystal structure of (-)-(5R,7R,8S,9R,10S)-8-methyl-7-[(5 R)-3-methyl-2-oxooxolan-3-en-5-yl]-1-aza-6-oxatricyclo[8.3.0.0 5,9 ]tridecan-13-one monohydrate

The title compound is an epimer of natural tetracyclic isosaxorumamide. The dihydrofuranone, oxolane, azepane and pyrrolidine rings adopt planar, twist, twist-chair and envelope forms, respectively. In the crystal, O—H⋯O hydrogen bonds connect the water and main molecules into a tape structure, which is further expanded into a three-dimensional network by C—H⋯O interactions.