Shin-ichi Nakatsuka

Epimerization of tea catechins under weakly acidic and alkaline conditions.

Tea catechins in a buffer at pH 7 with N2 replacing O2 epimerized rapidly at 80 °C with less than 10% of oxidative side reactions and gave catechin epimers in a 50–63% yield. The epimerization of catechins with three hydroxyl groups was faster than with two groups, and of galloyl-free catechins was faster than catechins with a galloyl ester.

Structures of dimers and trimers of 1-trimethylacetylindole produced in presence of aluminum chloride

Abstract The reactivity of 1-trimethylacetylindole 3 in the presence of aluminum chloride was studied and the structures of the products were determined as its dimers 4a – c and trimers 5c , etc.

Oligomerization of N-Tosylindole with Aluminum Chloride

The reactivity of N-tosylindole (4) in the presence of aluminum chloride was studied, and two types of oligomerization of 4 were observed. One type was condensation between both pyrrole parts (dimers 5 and 6 and trimer 7) and the other was between a pyrrole part and a benzene part of each indole nucleus (dimers 8 and 9).

Total synthesis of 0231B, an inhibitor of 3α-hydroxysteroid dehydrogenase produced by Streptomyces sp. HKI0231

The new inhibitors of 3α-hydroxysteroid dehydrogenase, 0231A 1 and 0231B 2, have a unique benz[c,d]indol-3(1H)-one structure in their molecules. In our advanced studies on indole chemistry, we have developed an efficient synthetic method for benz[c,d]indol-3(1H)-one derivatives. We report here its application to the synthesis of 0231B in 10 steps (8.1% overall yield) from 6-methylindole 8 by introducing an acyl group into the 3-position of the indole nucleus, cyclization of the side chain at the 3-position to the 4-position and subsequent elimination of the phenyl group, and conjugate addition of the substituted phenyl group.

ISOLATION AND STRUCTURE OF BZR-COTOXIN IV PRODUCED BY BIPOLARIS ZEICOLA RACE 3, THE CAUSE OF LEAF SPOT DISEASE IN CORN

Abstract BZR-cotoxin IV, a component of BZR-toxin produced by B. zeicola race 3, which causes leaf spot disease in corn, was isolated from the mycelia of the fungi and was determined to be a cyclic octadepsipeptide ( l ).

Novel oxidation products of cyanidin 3-O-glucoside with 2,2′-azobis-(2,4-dimethyl)valeronitrile and evaluation of anthocyanin content and its oxidation in black rice

The radical oxidation mechanism of anthocyanin derivatives was investigated by the reaction of cyanidin 3-O-glucoside in the presence of radical initiator 2,2-azobis-(2,4-dimethyl)valeronitrile (AMVN) in EtOH and aqueous CH3CN. Six different oxidation products were isolated, depending on the solvent employed. These products were identified using NMR spectroscopy and multistep derivatisation reactions. Of the products obtained, two novel oxidised anthocyanin derivatives were isolated from black rice under prolonged storage. A radical reaction mechanism is proposed on the basis of these reaction products. Quantification of oxidised anthocyanins in black rice is demonstrated as a method to verify freshness of the rice.

Isolation of Campesteryl Ferulate and Epi-Campesteryl Ferulate, Two Components of γ-Oryzanol from Rice Bran

Campesteryl ferulate (3a, 24R/α) and epi-campesteryl ferulate (3b, 24S/β), components of rice bran γ-oryzanol, were isolated by the preparative recycle HPLC system using a combination of ODS silica and cholester packed columns at over 99% purity. Their purities and structures of 3a and 3b thus obtained were confirmed by HPLC analysis and physical data (1H- and 13C-NMR, MS spectra, and X-ray crystallography).

Isolation of N,N-Dimethyl and N-Methylserotonin 5-O-β-Glucosides from Immature Zanthoxylum piperitum Seeds

Two serotonin derivatives, N,N-dimethylserotonin 5-O-β-glucoside (1a) and N-methylserotonin 5-O-β-glucoside (1b) were isolated from immature seeds of Zanthoxylum piperitum. Their structures were determined by multi-step conversion reactions and spectroscopic analyses. Immature seeds of Z. piperitum contained extremely high levels of compounds 1a and 1b of approximately 0.29% and 0.15% (w/w), respectively.

A SYNTHESIS OF 6-METHYLINDOLE DERIVATIVES BY METHYLTHIOMETHYLATION AT 6-POSITION IN INDOLE NUCLEUS

6-Methylindole derivatives were synthesized by introduction of methylthiomethyl group onto the 6-position of indole nucleus and subsequent desulfurization. Introduction of substituents on the benzene part (4-7 position) of indole ring is one of the most difficult problems in the organic syntheses1 We have developed several useful methods to resolve the problem and applied those to the syntheses of some natural products.2-4 ~ i l o m ~ c i n S is one of the most complicated natural products containing modified indole nucleus. All attempts toward total syntheses6 of mitomycins or its common structure: mitosenes4d. e. 7 started from substituted aniline and no synthetic route toward mitomycins from simple indole have been appeared. Mitomycin A X=OCH3 (I), C X=NH2 (2) 256 HETEROCYCLES, Vol. 41, NO. 2, 1995 We have been reported efficient methods for the synthesis of indolcquinone4ac and applied them for the synthesis of 7-methoxymitosene (4) starting from 6-methylindole (3).4d, e In this paper, we report a novel method for the synthesis of 6-methylindole derivative by methylation at 6-position of indole nucleus. Although Friedel-Crafts a ~ ~ l a t i o n ~ ~ ? C. of methyl indole-3-carboxylate (5) afforded corresponding 5and 6-monoacyl derivatives in reasonable yields, Friedel-Crafts alkylation of 5 gave only small amount of 5and Galkylated products. Fof the synthesis of mitomycin, we tried methylation of methyl I-methylindole-3carboxylate (6) by CH3BrIAIC13, (CH3)2S04/AIC13 etc, but no desired methylated product was obtained. On the other hands, Friedel-Crafts alkylation of 6 using stabilized alkylating agent: chloromethyl methyl sulfide (5 eq. CICH2SCH3)15 eq. AIC13 at 2S°C for 1 h gave desired monoalkylated products (N and 9) as unseparahle mixture in 28% yield(l:l). X; 1 ~ n m r (CDC13) B(ppm) 2.02 (3H, hr s), 3.82 (3H, s), 3.83 (2H, s), 3.90 (3H, s), 7.23 (IH, br d, J=8.2 Hz), 7.26 (IH, s), 7.78 (IH, s), 8.09 (IH, d, 14 .2 Hz). 9; 1 ~ n m r (CDC13) B(ppm) 2.00 (3H, s), 3.82 (3H, s), 3.84 (2H, s), 3.91 (3H, s), 7.29-7.34 (2H, m), 7.76 (IH, s), 8.04 (IH, s). Desulfurization of N and 9 was achieved with Raney Ni to give 5and 6-methyl derivatives (10 and 11) in 90% yield but those were also unseparahle on silica gel tlc or column chromatography. N-Renzyl derivative (7)9 was obtained by benzylation of 5 with BnRrIK2CQ in DMF in 96% yield. Bromination of 7 with 1.5 eq. Rr2 at 0°C for 2 h afforded 5-bromo derivative (13,11 31 %) with its 6-bromo isomer (12,1° 61 %). Those were easily separated on silica gel column chromatography. The brominated positions of 12 and 1,3 were easily determined by l ~ n m r spectra [H-4 pro tor^ signal. 12; 8.05 ppm (IH, d, J=8.6 Hz), 1-1; 8.33 ppm (IH, d, J=l.8 ~z)l.ac. 8 Methylthiomethylation of 1.7 with 1.2 eq. CICH2SCH3A eq. AIC13 in CH2C12 at -20°C for 30 min was very clean and 6-methylthiomethyl derivative (14j12 &as ohtained in 91 % yield after short column chromatography using silica gel. We understand that bromine atom at the 5-position of 13 accelerated the reactivity of the 6-position and alkylating yield was very high. Not only desulfurization but also debromination of 14 with Raney Ni in methanol at ?5OC for 10 min gave desired 6-methylindole derivative (15,13 76%). ~emoval of N-benzyl group of 15 was achieved with AIC1.7 in C H ~ C I ~ at 2S°C to give methyl 6-methylindole-3-carboxylate (16,l4 87%). Consequently, methyl group was introduced at the 6-position of indole nucleus by (I) bromination, (2) methylthiomethylation, (3) HETEROCYCLES, VOI. 41, No. 2,1995 257 5 R=H Unseparable mixture of 8 and 9 Unseparable mixture of 10 and 11 6 R=CH3 8 R1=CH2SCH3, R2=H 10 Rl=CH3, R2=H 7 R=Bn 9 R1=H. R2=CH2SCH3 11 RI=H, R2=CH3 Reagents: a) CICH2SCH3. AIC

ISOLATION AND STRUCTURE DETERMINATION OF LACCAIC ACID F FROM LAC-DYE PRODUCED FROM THAI STICKLAC

(28%); b) Raney Ni (90%); c) BnBr, K2CO3 (96%); d) Br2 (12; 61%. 13; 31%); e) CICH2SCH3, AICI3 (91%); f ) Raney Ni (76%); g) AIC13 (87%); h) BrCH&H2CH2CI. K&03 (94%). reduction with Raney Ni in 21 % over all yield (7-15). Then, 6-methylindole derivative (16) was treated with Br(CH2)3CI/K2C03 in DMF to afford Nchloropropyl derivative (17) in 94% yield.4e Since we reported a synthetic route toward 7-methoxymitosene (4) from 17 as a key intermidiate, we could establish an improved route to 4. By combination of those results and the previous publication. we could introduce all functional groups found in 7-methoxymitosene (4) in a simple indole (5). Further synthetic studies toward mitomycins are now in