Yoshimitsu Nagao

Reactions of vinylsilanes with lewis acid-activated iodosylbenzene: stereospecific syntheses of vinyliodonium tetrafluoroborates and their reactions as highly activated vinyl halides

Abstract Alkenyl(phenyl) iodonium tetrafluoroborates 3 were synthesized from alkenylsilanes 1 by the reaction with iodosylbenzene and boron trifluoride-diethyl ether or triethyloxonium tetrafluoroborate. The reaction proceeds stereospecifically with retention of configuration of 1 . X-ray diffraction analysis of (4-tert-butylcyclohexenyl)phenyliodonium tetrafluoroborate ( 3b ) revealed the highly ionic structure with the distorted T-shape arrangement. Iodonium salts 3 behave like the highly activated species of vinyl iodides due to the high leaving ability of the iodine(III) substituents. Thus, a variety of substituted olefins including α-cyano and α-nitro olefins, vinyl sulfides, vinyl halides, and α,β-unsaturated esters, were synthesized from 3 under mild conditions. A ligand coupling mechanism via the formation of 10-I-3 intermediate 27 containing a copper(III) ligand is proposed for the substitutions of 3 with nucleophiles.

Tumor inhibitors having potential for interaction with mercapto enzymes and/or coenzymes

Abstract On the basis of extensive information on in vivo metabolism as well as biomimetic reactions using simple SH compounds and some enzymes, numerous chemical functions which react with SH groups are divided into two classes; i.e., one which involves electrophilic addition (EA) to an SH group and the other which features displacement reactions (DR) by the SH group (see Tables 1 and 2). The known tumor inhibitors are accordingly classified into EA and DR types. Biomimetic reactions of tumor inhibitors with model compounds of SH enzymes (or coenzymes) and with some SH enzymes themselves are described. Finally, as enhancement factors for the antitumor activity, the roles of hydrogen-bonding, neighboring group participation, and effect of ester side chains are introduced. These discussions may serve in the development of the new SH alkylating antitumor agents.

The antitumor and antibacterial activity of the Isodon diterpenoids.

Oridonin (1), lasiokaurin (2), enmein (8), and enmein-3-acetate (9) and related compounds (3 and 10, ) all of which have α-methylene cyclopentanone function in their molecule, have been shown to have antitumor activity against Ehrlich ascites carcinoma inoculated into mice. These compounds have also indicated specific activity against gram-positive bacteria. On the other hand, oridonin dihydro-derivative (4), compound (5), trichokaurin (6), and dihydroenmein (11) show any activity against neither tumor nor bacteria. Thus, it is concluded that the α-methylene-cyclopentanone system must be an important active center. Biomimetic reactions of oridonin and enmein with several thiols etc. support this conclusion.

GENERATION OF BETA -(PHENYLSULFONYL)ALKYLIDIENECARBENES FROM HYPERVALENT ALKENYL- AND ALKYNYLIODONIUM TETRAFLUOROBORATES AND SYNTHESIS OF 1-(PHENYLSUL FONYL)CYCLOPENTENES

Michael-type addition of benzenesulfinic acid to alkynyl(phenyl) iodonium tetrafluoroborates in methanol gives stereoselectively (Z)-(β-(phenylsulfonyl) alkenyl) iodonium tetrafluoroborates in high yields. [β-(Phenylsulfonyl) alkylidene] carbenes derived from the (Z)-(β-(phenylsulfonyl) alkenyl) iodonium tetrafluoroborates by base treatment predominantly undergo intramolecular 1,5-carbon-hydrogen insertions to give 1-(phenylsulfonyl) cyclopentenes along with a small amount of rearranged alkynes, which is in a marked contrast with the facile 1,2-migration of β-(phenylsulfenyl) and β-(phenylsulfinyl) groups of alkylidenecarbones. Reaction of alkynyl(phenyl) iodonium tetrafluoroborates with benzenesulfinates directly affords 1-(phenylsulfonyl) cyclopentenes via tandem Michael-carbene insertion reactions. The mechanism of 1,2-migration of [β-(phenylsulfonyl) alkylidene] carbenes is also discussed

Antitumor activity of the isodon diterpenoids: Structural requirements for the activity

A significant antitumor activity of oridonin (1) and lasiokaurin (2), the kaurene-type diterpenoids ofIsodon species, was shown by their i.p. injection to the test mice inoculated by Ehrlich ascites carcinoma. Enmein (8), compounds9 and3 were also active under larger dose. Subsequently, the relationship between their chemical structure and antitumor activity was investigated, and the activity of oridonin (1) and lasiokaurin (2) was rationalized in terms of their structural feature.

Hypervalent iodine oxidation of amines using iodosobenzene: synthesis of nitriles, ketones and lactams

Primary aliphatic amines on oxidation with iodosobenzene in CH2Cl2 or H2O yield the corresponding nitriles, while primary cycloalkylamines give the corresponding cyclic ketones. Lactams are obtained by the oxidation of cyclic amines. (S)(−) Nicotine (15) is oxidized to (+)-cotinine (16). The intermediary imine involved in these processes was trapped in the case of piperidine as the α-aminonitrile.

Monitored aminolysis of 3-acylthiazolidine-2-thione : A new convenient synthesis of amide

Abstract 3-Acylthiazolidine-2-thiones ( 1 ) were easily prepared and they were treated with several amines in dichloromethane to give amides 4 in very high yields within a short time. Aminoalcohols and aminophenols were selectively converted into acylaminoalcohols and acylaminophenols, respectively, by this reaction. One can monitor the reaction by disappearance of the yellow color of the starting material 1 . Some amide alkaloids ( 1 5 – 1 8 ) have effectively been synthesized.

ASYMMETRIC TOTAL SYNTHESIS OF ISP-I (MYRIOCIN, THERMOZYMOCIDIN), A POTENT IMMUNOSUPPRESSIVE PRINCIPLE IN THE ISARIA SINCLAIRII METABOLITE

Abstract Asymmetric total synthesis of ISP-I has been achieved by utilizing highly selective E -olefin formation based on the Schlosser-modified Wittig reaction and highly diastereoselective aldol reactions employing both chiral heterocyclic derivatives, 3-acetyl-(4 S )-isopropyl-1,3-thiazolidine-2-thione and ethyl [(5 R )-2,5-dihydro-5-isopropyl-3,6-diethoxypyrazin]-2-yl carboxylate.

Reaction of alkynyltrimethylsilanes with a hypervalent organoiodine compound: A new general synthesis of alkynyliodonium salts

Abstract New general methods for the synthesis of alkynyl(phenyl)iodonium tetrafluoroborate 2 from alkynyltrimethylsilanes 1 utilizing the combination of iodosylbenzene and triethyloxonium tetrafluoroborate or boron trifluoride etherate were developed. The medium effect observed in the reaction was also discussed.

Vinyliodonium salts : their stereospecific synthesis and reactions as the activated vinyl halides

Abstract Vinyliodonium salts 2 were synthesized from vinylsilanes 1 by the reaction with iodosylbenzene and triethyloxonium tetrafluoroborate. The reaction occurs stereospecifically with retention of configuration. Vinyliodonium salts 2 are highly effective as the activated species of vinyl iodides. Thus, a variety of substituted olefins including α-cyano and α-nitro olefins, vinyl sulfides, vinyl halides, and α,β-unsaturated esters, were prepared from 2 under mild reaction conditions.