Masatoshi Nagamochi

A novel and efficient route to chiral A-ring aromatic trichothecanes—The first enantiocontrolled total synthesis of (-)-debromofiliformin and (-)-filiformin

Abstract The first examples of asymmetric dihydroxylation (AD) of the cyclopropylidene derivatives 12a∼e followed by enantiospecific 1,2-rearrangement of the resulted diols 13a∼e to give the optically active cyclobutanones 15a∼d and 11, and also the first enantiocontrolled total synthesis of (-)-debromofiliformin (7a) and (-)-filiformin (7b) starting from 11 via the regiocontrolled cyclization of the phenolic allyl alcohol 25 to the A-ring aromatic trichothecane 26, were reported.

Design, synthesis, and biological evaluations of novel 7-[7-amino-7-methyl-5-azaspiro[2.4]heptan-5-yl]-8-methoxyquinolines with potent antibacterial activity against respiratory pathogens.

Novel 7-[7-amino-7-methyl-5-azaspiro[2.4]heptan-5-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]- 8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 2a and 2b were designed and synthesized to obtain potent antibacterial drugs for the treatment of respiratory tract infections. Among these, compound 2a possessing (S)-configuration for the asymmetrical carbon on the pyrolidine moiety at the C-7 position of the quinolone scaffold exhibited potent in vitro antibacterial activity against respiratory pathogens including gram-positive (Streptococcus pneumoniae and Staphylococcus aureus), gram-negative (Haemophilus influenzae and Moraxcella catarrhalis), and atypical strains (Chalmydia pneumoniae and Mycoplasma pneumoniae), as well as multidrug-resistant Streptococcus pneumoniae and quinolone-resistant and methicillin-resistant Staphylococcus aureus). Furthermore, compound 2a showed excellent in vivo activity against the experimental murine pneumonia model due to multidrug resistant Streptococcus pneumoniae (MDRSP) and favorable profiles in preliminary toxicological and nonclinical pharmacokinetic studies.

A concise enantiocontrolled total synthesis of (-)-α-bisabolol and (+)-4-epi-α-bisabolol

Abstract The regiocontrolled hydrogenation of the cyclohexadiene 6, synthesised from the chiral cyclobutanone 3 was effectively achieved with [1,4-bis(diphenylphosphino)butane](1,5-cyclooctadiene)rhodium (1) tetrafluoroborate as catalyst to give the olefins 7 and 8 which were converted into (−)-α-bisabolol 1a and (+)-4-epi-α-bisabolol 15via9 and 10, 11 and 12, and 13 and 14.

An Enantiocontrolled Formal Total Synthesis of (+)-Ipomeamarone, (-)-Ngaione, and Their Epimers

A concise enantiocontrolled synthesis of (+)-(5S, 2R)- and (+)-(5R, 2R)-5-(3-furyl)-2-iodomethyl-2-methyloxolanes, (6) and (5), was achieved starting from (+)-(R)-2-hydroxymethyl-2-methylcyclobutanone (11) which was efficiently prepared by the tandem asymmetric epoxidation and 1,2-rearrangement of 2-cyclopropylidenepropanol (9). This constitutes an enantiocontrolled formal total synthesis of (+)-ipomeamarone (1), (+)-epiipomeamarone (2), (-)-ngaione (3) and its epimer (4)

Chiral cyclobutanones as versatile synthons: the first enantioselective total synthesis of (+)-laurene

A novel and convenient route to the thermodynamically unstable ketone 11via the cyclopentanone 8 which was synthesised by palladium-mediated ring expansion of the chiral siloxyvinylcyclobutanes 9 and 10 has been developed. This leads to an enantioselective total synthesis of (+)- laurene 1.

The first enantioselective total synthesis of (+)-laurene

The cyclopentenone 8, synthesised by palladium mediated ring expansion of the chiral vinylcyclobutanols 3 and 4, is converted to the thermodynamically unstable ketone 16 which on methylenation gives (+)-laurene 1.