Pyrido benzothiazepines

The reduced pyrido[4,3-g][l,4]benzothiazepine 133 has been detected by HPLC as a novel metabolite in some human urine samples. It arises from Pictet-Spengler condensation of 5-S-cysteinyldopa with formaldehyde. This chemistry also underpins a facile synthesis of the 2,3,4,5-tetrahydro[l,4]benzothiazepine 134 via reaction of formaldehyde with a cysteinylcatechol . 

Syntheses of four different condensed pyrido-l,5-benzothiazepine systems are described in the literature. Several publications concerning pyr-ido[2,3-b][l,5]benzothiazepines are known, but only one synthetic approach was reported for each of the other systems investigated. 

The synthesis of 7,9-dihydro-6//-pyrido[2,l-rf][l,5]benzothiazepines (115) was carried out by reaction of 93 with acetone or 2-butanone in the presence of p-toluenesulfonic acid. The reaction also afforded compounds 116 and 117, which were detected by GC/MS analysis and not isolated (Scheme 35) (89LA601). 

The first available review of annelated 1,5-benzothiazepines, a diverse group of increasingly important polycycles, is provided by A. Chimirri and her colleagues (Messina, Italy) in Chapter 2. Recent developments in the chemistry of pyrido[l,2- ]pyrimidines are covered in Chapter 3 by... 

The novel fused heterocyclic system pyrazolo[4, 3 5,6]pyrido-[2,3-b]-1,5-benzoxepine (53) and its benzothiazepine analogue have been obtained by cyclisation of a substituted pyrazolo[3,4-b]-pyridine derivative. 

Tricyclic systems as compounds of potential pharmacological interest prepared by conventional cyclisation procedures include thienoanellated [l,4]benzoxazepines <94JHC1053>, pyrido[l,4] and [l,5]benzoxazepines and thiazepines <94JMCS19>, and IH- and 2H-pyrazolo[3,4-c][2,l]benzothiazepines <94JHC93>. A number of... 

Jhh and " Jhh couplings have been measured by Katrizky et al for re-gioisomeric 3-[2- or 5-anilino-2-(alkylamino)phenyl]propanoic acids, 2H-1,4-benzothioazin-3(4/f)-ones and 2,3-dihydro-l,5-benzothiazepin-4(5if)-ones, by Suri et for a series of pyrido[l,2-a]pyrimidine derivatives, and by Laatsch and co-workers for helquinoline, a new tetrahydroquinoline antibiotic isolated from Janibacter limosus. The configuration around the double bonds and the epoxide stereochemistry of oximidine III, a new antitumor antibiotic against transformed cells from Pseudomonas sp., has been established on the basis of Vhh by Hayakawa et... 

---