The author and his group have been developing new reactions based on molecular structure characteristics; sigma-symmetric bifunctional molecules, dipole-dipole repulsion, active
amide structures, latent active species, orbital-orbital interactions, nonbonded interactions, strained structures, allenic structures, etc. Various new reactions such as asymmetric aminolyses and Dieckmann-type cyclizations of prochiral sigma-symmetric dicarboxylic diamides, asymmetric
aldol-type reactions onto gamma-hydroxybutenolides and asymmetric
imine alkylations onto omega-acetoxy
lactams using chiral Sn(II) enolates, asymmetric Pummerer-type reactions, cascade reactions and endo-mode cyclizations exploiting alpha,beta-unsaturated allenic
esters and
ketones, base- and
palladium-promoted ring-expansion reactions, and syntheses of alpha-substituted serines and 1-azabicyclo [1.1.0]
butane have been achieved. These new reactions were applied to the synthetic development of new seed and lead compounds (SH-
enzyme inhibitors,
tumor inhibitors, and
antibiotics) with the aim of synthesizing new drugs. Asymmetric syntheses of (+)-Prelog-Djerassi lactonic
acid methyl
ester, (+)-
carbacyclin, ISP-I (
myriocin), (+)-
conagenin,
Geissman-Waiss lactone,
biapenem (a new
carbapenem antibiotic),
thienamycin-like gamma-
lactam, and bicyclic
alkaloids were also achieved by utilizing these reactions. Evaluation and molecular design of the seed and model compounds for
angiotensin II receptor antagonists,
tumor inhibitors, and
antibiotics have been investigated on the basis of QRSA and/or nonbonded S...X (X=O, N, S,
halogens) interaction concepts.