Mayumi Nishida

FIXATION OF ATMOSPHERIC NITROGEN : SYNTHESIS OF HETEROCYCLES WITH ATMOSPHERIC NITROGEN AS THE NITROGEN SOURCE

Dry air is the source of molecular nitrogen for reactions with TiL4 , Li, and TMSCl (L = Cl, OiPr; TMS = trimethylsilyl). The nitrogen-titanium complexes thus prepared can be used to synthesize indoles, pyrroles, and lactams from carbonyl compounds. Applying this method to 1 provides access to 2, the key compound in the synthesis of (±)-lycopodine.

A simple preparation of (R)-(2-cyclopentenyl)acetic acid and (R)-(2-cyclohexenyl)acetic acid using β-diastereoselective radical cyclization in the presence of Lewis acid

Abstract The alkenyl radical generated from (−)-8-phenylmenthyl 7-iodo-2,6-heptadienoate smoothly cyclized to afford ( R )-(2-cyclopentenyl)acetate with 88% de in 90% yield. ( R )-(2-Cyclohexenyl)acetate was also obtained with 84% de in 72% yield under the same conditions. The presence of Lewis acid is essential for high diastereoselectivity and chemical yield.

Radical cyclization using a thioacetal group for radical generation

Abstract The generation and cyclization of several heterocyclic radicals were investigated. The hydrogen abstraction from 1,3-dithiane, 1,3-dithiolane, and 1,3-oxathiane rings by a benzophenone triplet generated the corresponding heterocyclic radicals, which gave the cyclized products by intramolecular addition to α,β-unsaturated esters. Diastereoselective radical cyclization using chiral acetals was also investigated.

Generation and intramolecular cyclization of free radicals at the carbon between two heteroatoms under non-reductive conditions

Abstract Dithioacetal group was found to be a good radical generating group in the presence of photo-excited benzophenone and the resulting radical could be trapped in the intramolecular manner to give cyclopentanone and cyclohexanone derivatives.

Annexin 5 Messenger Ribonucleic Acid Expression in Pituitary Gonadotropes Is Induced by Gonadotropin-Releasing Hormone (GnRH) and Modulates GnRH Stimulation of Gonadotropin Release

Our previous studies on annexin 5, a member of the annexin family of proteins, have shown its expression in the anterior pituitary gland, its preferential distribution in gonadotropes, and its increase after ovariectomy. In the present study, we examined (1) whether annexin 5 is synthesized in gonadotropes, (2) whether its expression is under the control of gonadotropin-releasing hormone (GnRH), and (3) the effect of annexin 5 on gonadotropin release. Large cells, also called castration cells, appeared in anterior pituitary tissue 3 weeks after ovariectomy. These cells have been confirmed to be hyperfunctioning gonadotropes and are easily discriminated from other pituitary cells without immunostaining. Using in situ hybridization with a digoxigenin-labeled ribonucleic acid probe, enhanced expression of annexin 5 messenger ribonucleic acid (mRNA) in these gonadotropes was clearly demonstrated. Northern blot analysis showed an increase in the level of annexin 5 mRNA expression 3 weeks after ovariectomy. It was lessened 3 h after the injection of Cetrorelix (GnRH antagonist, 10 µg i.v.). Administration of a GnRH analog [GnRHa; Des-Gly 10 (Pro9) GnRH ethylamide, 0.2 ml of 2.5 µg/ml saline ten times intraperitoneally at 30-min intervals] significantly increased pituitary annexin 5 mRNA. In primary cultures of anterior pituitary cells, recombinant rat annexin 5 stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in a dose-dependent manner. Concomitant administration of annexin 5 (1 µg/ml) and GnRHa augmented the LH and FSH release induced by GnRHa. After a 1-hour incubation, cycloheximide (10 µg/ml) apparently inhibited the LH response to GnRHa, while annexin 5 (2 µg/ml) moderated this inhibition. Further, the antisense oligodeoxynucleotide to annexin 5 mRNA blunted the LH response to GnRHa. It is thus concluded that annexin 5 is synthesized in the gonadotropes under the effect of GnRH, and it is suggested that annexin 5 synthesis mediates at least partly GnRH receptor signaling to stimulate gonadotropin secretion.

Novel skeletal rearrangement of hydroindan derivatives into hydroazulenones via an alkoxy radical

A novel construction of hydroazulenones using skeletal rearrangement of epoxy-hydroindan derivatives via alkoxy radical was developed. The reaction was also found to proceed without damage of acetal or olefin group.

Total synthesis of schizocommunin and revision of its structure.

A proposed structure for schizocommunin (Z)-1(hydroxy) and its geometric isomer (E)-1(hydroxy), which exist in a keto form, has been synthesized. However, the spectroscopic data of (Z)-1(keto) and (E)-1(keto) were not consistent with those reported for natural schizocommunin. After reinvestigating the spectral data for natural schizocommunin, we synthesized the quinazolinone derivative (Z)-2 as a revised structure for schizocommunin. All of the spectral data of (Z)-2 were completely identical to those reported for natural schizocommunin. (Z)-2 showed moderate antiproliferative activity.

Skeletal Rearrangement via Alkoxy Radical: Conversion of Epoxydecalin Thiocarbonylimidazolides to Bicyclo[6.3.0]undecanones and Bicyclo[5.3.1]undecanones

Abstract The skeletal rearrangement of five types of epoxydecalin thiocarbonylimidazolides was investigated. This reaction proceeded via a 10-membered cyclic carbon radical formed by β-cleavage of alkoxy radicals, and produced two types of skeletal rearranged products; i.e. bicyclo[6.3.0]undecanones and bicyclo[5.3.1]undecanones. The ratio of the products strongly depended on the character and stereochemistry of the substituents.

A simple preparation of the hydroazulene skeleton from cyclopentanone derivatives via a free radical process

Abstract The hydroazulene skeleton (bicyclo[5.3.0]decane) was prepared from 2-(pent-4-ynyl)cyclopentanones in a single step by a free radical reaction. The efficiency of the conversion was greatly influenced by the substituents on the cyclopentane ring and on the side chain.

Diastereoselective radical cyclization using a chiral α-methyl-α,β-unsaturated ester: Controlling the stereochemistry at both the α- and β-positions

Abstract Diastereoselective radical cyclizations of (−)-8-phenylmenthyl 2-methyl-2-octene-7-ynoate ( 9 ) and (−)-8-phenylmenthyl 7-iodo-2-methyl-2,7-octadienoate ( 10 ) were investigated. The best results were obtained in the cyclization of 10 at −98°C. A mixture of four diastereomers was obtained at a yield of 72% and with a diastereoselectivity of 78:12:9:1. The main product was ( S )-2-[( R )-2-methylene-cyclopentyl]propionate ( 3a ). The diastereoselectivities at the α- and β-positions were 90:10 and 79:21, respectively.