Anomalous substituent effects in the bischler-napieralski reaction of 2-aryl aromatic formamides

Treatment of some 1-naphthylformamides (or formanilides) possessing a 2,4,5-trioxygenated phenyl substituent at the 2-position with POCl(3) caused an unprecedented carbon insertion reaction into a benzene ring, producing 7-5 ring (azaazulene) systems as valence isomers of isoquinoline skeletons. Precise examination of this abnormal Bischler-Napieralski reaction (BNR) using various substrates led to the following scope and limitations: (i) the 7-5 ring systems were constructed when either 2-alkoxy-4, 5-methylenedioxyphenyl- or 4,5-dialkoxy-2-hydroxyphenyl-substituted formamides were used as a starting substrate; (ii) in the former case the formyl carbon was inserted into the C(1)-C(6) bond of the 2-phenyl group, and normal isoquinoline cyclization competed with an abnormal carbon insertion reaction; (iii) the presence of a hydroxy group at the 2'-position as in the latter cases caused exclusive carbon insertion, in which alternative C(1)-C(2) insertion products were quantitatively formed; (iv) 3, 6-dimethoxy-2-hydroxyphenyl-substituted formanilide electronically equivalent to 4,5-dialkoxy-2-hydroxy derivatives produced an indole-pyrone as an abnormal BNR product. Theoretical approaches using the PM-3 method indicated that these abnormal BNRs could be triggered by ipso attack at the 1'-position yielding spiro intermediates. Ring cleavege of the six-membered ring in the spiro intermediates to a ketene function followed by recyclization was proposed for the 2'-hydroxy-directed abnormal BNRs leading to the C(1)-C(2) insertion product or the indole-pyrone derivative.

Organization and nucleotide sequences of ten ribosomal protein genes from the region equivalent to the S10 operon in the archaebacterium, Halobacterium halobium.

A determination was made of the nucleotide sequence of the 7340-bp region of a ribosomal protein gene cluster of Halobacterium halobium, which is equivalent to the S10 operon of Escherichia coli. The sequence was analyzed with the codonpreference program deduced from the halobacterial codon usage table that showed a very high GC content of the third codon position. The sequence was comprised of a string of 13 tightly linked ORFs. Most of the ORFs were homologous with ribosomal protein genes (ORF1-ORF2-rpl3-rpl4-rpl23--rpl2- rps19-rpl22-rps3-rpl29-ORF11-rps17-r pl14). The 13-gene string was preceded by three putative AT-rich promoter sequences. The order of the genes in H. halobium essentially agreed with that of the corresponding genes of E. coli (S10-operon), except for certain deletions or insertions of additional protein genes.

Synthetic anthracyclines: regiospecific total synthesis of D-ring thiophene analogues of daunomycin.

The key anhydride 2-acetoxy-[2-carboxy-5-(trimethylsilyl)thiophen-3-yl]acetic acid anhydride (8), prepared from (2-carboxythiophen-3-yl)acetic acid (5), underwent a strong base-induced cycloaddition reaction with the chloroquinone acetal (11) to give the 7,7-ethylenedioxy-2-trimethylsilyl-6,7,8,9- tetrahydroanthra[2,3-b]thiophene-5,10-dione (12) regioselectively. Similarly, the regioisomeric 8,8-ethylenedioxy-2-trimethylsilyl-6,7,8,9-tetrahydroanthra[2,3-b] thiophene- 5,10-dione (30) was obtained by the strong base-induced cycloaddition reaction of 8 with the chloroquinone acetal (29). These cycloadducts (12 and 30) were converted to D-ring thiophene analogues (28 and 38) of daunomycin (1a). Another D-ring thiophene analogue (42) which has a trimethylsilyl substituent in the D-ring was also prepared.

Synthetic anthracyclines: regiospecific total synthesis of a D-ring indole analogue of daunomycin.

The 4-methoxy-5-methylpyrano[4,3-b]indole-1,3(4H,5H)-dione (9), prepared from methyl 3-methoxycarbonyl-1-methylindol-2-yl acetate (6), underwent a strong base-induced cycloaddition reaction with 2-chloro-6,6-ethylenedioxy-5,6,7,8-tetrahydro-1,4-naphthoquinone (11) to give the tetrahydronaphtho[2,3-b]carbazole-7,12-dione (10), regioselectively. The cycloadduct (10) was successfully converted to a D-ring indole analogue of daunomycin (1a).

Analysis of amlodipine in serum by a sensitive high-performance liquid chromatographic method with amperometric detection.

An analytical method for a new calcium channel blocking agent, amlodipine, has been developed using high-performance liquid chromatography with electrochemical detection. No compound modification is required for detection and the calibration curve in spiked sera is linear and reproducible over the range 0.2-2.0 ng ml-1. The method has been applied successfully to pharmacokinetics studies in rats and also can be used for other dihydropyridine compounds such as nifedipine and nicardipine.