The Synthesis of Linearly Annelated Polycyclic Ketones by Friedel-Crafts Rearrangements of Their Angular Isomers

Derivatives of 5H-dibenzo[a, d]cycloheptene carrying an alkylamine side chain at position 5 serve as useful drugs in the chemotherapy of mental diseases.^1–2 During a study of the effect of annelation on the activity of these psychopharmacological agents of the amitryptyline type, it was deemed necessary to synthesize the linear 13,14-dihydro-6H-cyclohepta-[1,2-b:4,5-b']dinaphthalen-6-one (I). The method of approach was the general synthesis of the polycyclic skeleton of amitryptyline, in which the seven-membered ring is constructed by a Friedel-Crafts (F - C) intramolecular acylation.^3–4 Ketone I, however, contains two 2,3-disubstituted naphthalene moieties condensed to the central seven-membered ring.     

Design and Synthesis of Linearly Fused Triquinanes through Tandem-Metathesis: Access to Basic Core of Cucumin,Capnellene, Chondrosterin,and Xeromphalinone

Herein, a short synthetic approach to linearly fused tricyclic enone 1 and cis-anti-cis type hydroxy-triquinane 2 has been described in an efficient manner by employing tandem-metathesis as a key step. The triquinane-based enone 1 is prepared by a Babler–Dauben oxidation of hydroxy-triquinane 2 , which is assembled by following a three-step sequence involving a regio- and stereoselective allylation, vinyl Grignard addition, and tandem-metathesis. Our strategy relies on exo-tricyclic ketone, which is derived from readily available exo-dicyclopentadiene-1-one. The newly synthesized molecules were identified and characterized by nuclear magnetic resonance spectroscopy (NMR), and high-resolution mass spectrometry (HRMS) data. It is worth mentioning that tricyclic enone 1 is present as a core unit of many naturally occurring polyquinanes, particularly xeromphalinone family members. Hence, our approach may be useful in the synthesis of such bioactive molecules.     

A Convenient Synthesis of New Annelated Pyrimidines and Their Biological Importance

Several bicyclic/tricyclic‐fused pyrimidines were synthesized from the reactions of amino esters and bifunctional nucleophiles such as 2‐methylthio‐thiazoline and 2‐methylthio‐imidazoline. The synthesized compounds were tested for their in vitro antimicrobial activities that revealed mild to moderate growth inhibitory potentials.     

A Convenient Synthesis and Pharmacological Activity of Novel Annelated Pyrimidine Derivatives

Simple and convenient synthesis for a series of 2,3‐diglycosylpyrimidine 4 , pyrazolo[3,4‐d]pyrimidine 8 , ditetrazolo[1,5‐a;1′,5′‐c]pyrimidine 9 , 2,9a,10‐triazaanthracene 12 , thieno[2,3‐d]pyrimidine 14 , 1,3,5,7‐tetraazafluorene‐8‐one 15 , 1,3,5‐triazafluorene‐8‐one 16 , 1,3‐diazafluorene 21a,b derivatives have been synthesized via a sequence of heterocyclization reactions of suitably functionalized 6‐[5‐(4‐bromophenyl)ox‐azol‐4‐yl]‐4‐oxo‐2‐thioxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carbonitrile ( 2 ) with different electrophiles and nucleophiles. The new compounds were prepared with the objective to study their pharmacological properties.     

Synthesis and Antimicrobial Activity of Some Annelated Quinazoline Derivatives

A highly efficient and versatile synthetic approach to the synthesis of annelated quinazoline derivatives viz 1,2,4‐triazino[4,3‐c]quinazoline 5–7 , 11 , thiazolidinylquinazoline 9 , quinazolino[4,3‐b]quin‐azolin‐8‐one 12 and imidazoquinazolines 14a,b,15 is presented. Also, a variety of pyrazolylquinazolines 19–21 and pyrimidinylquinazolines 22a,b were obtained via a sequence of heterocyclization reactions of 4‐methyl‐N‐[4‐(4‐oxo‐3,4‐dihydroquinazolin‐2‐yl)phenyl]benzene‐sulfonamide ( 2 ) with different reagents. The new compounds were synthesized with the objective of studying their antimicrobial activity.     

Synthesis and Pharmacological Activity of Annelated Pyrimidine Derivatives

A series of 1-glycosyl-2-glycosylthiopyrimidine (4), annelated pyrimidine derivatives, pyrazolo[3,4-d]-pyrimidine (8), ditetrazolo[1,5-a;1‘,5‘-c]pyrimidine (9), 2,9a,10-triazaanthracene (12), thieno[2,3-d]pyrimidine (14),9-thia-1,3,5,7-tetraazafluorene-8-one (15), 7-oxa-9-thia-1,3,5-triazafluorene-8-one (16), 5-oxa-9-thia-1,3-diaza-fluorene (21a and 21b) derivatives have been synthesized via a sequence of heterocyclization reactions of suitably functionalized 6-[5-(4-bromophenyl)oxazol-4-yl]-1，2，3，4-tetrahydro-2-thioxo-4-oxopyrimidine-5-carbonitrile (2) with different electrophiles and nucleophiles. The new compounds were prepared with the objective to study their pharmacological properties.     

Synthesis and Pharmacological Activity of Annelated Pyrimidine Derivatives

A series of 2,3-diglycosylpyrimidine 4, annelated pyrimidine derivatives, pyrazolo-[3,4-d]pyrimidine 8, ditetrazolo[1,5-a; 1′5′]pyrimidine 9, 2,9a,10-triazaanthracene 12, thieno- [2,3-d]pyrimidine 14, 9-thia-1,3,5,7-tetraazafluorene-8-one 15, 7-oxa-9-thia-1,3,5-triazafluorene-8-one 16, and 5-oxa-9-thia-1,3-diazafluorene 21a , b derivatives have been synthesized via a sequence of heterocyclization reactions of suitably functionalized 6-[5-(4-bromophenyl)oxazol-4-yl]-1,2,3,4-tetrahydro-2-thioxo-4-oxopyrimidine-5-carbonitrile (2) with different electrophiles and nucleophiles. The new compounds were prepared with the objective to study their pharmacological properties.     

The Tricyclooctanone Approach to the Total Synthesis of Steroids. The Cyclization of the A-CD Unit

The first steps of a novel approach to the total synthesis of 9, 11-dehydroestrone via tricyclo[3.3.0.0^2,8]octan-3-one (2) are described. One route involves a tandem-type transformation of the key intermediate 3 (A-CD unit) consisting of cyclopropane cleavage and ring B closure to afford C, 18-bisnor-13 α, 17 α-estradiol derivatives. E.g. the 3-methoxy-9 ζ-hydroxy-17 α-methanesulfonyloxy derivative (-)- 6 has been synthesized in 8 steps and 10% overall yield from 1,3-cyclohexadiene. As an alternative, the A-CD type intermediate 4b has been prepared and could be used for a ring C enlargement prior to cyclization.     

Synthesis and X-Ray Crystal Structure of an Annelated Spirophosphorane

Abstract

Reaction of the 2-azidoalcohol 1 with 2-phenyl1-1,3,2-dioxaphospholane leads to a 4:1 mixture of the pentacoordinate phosphorane 3 and the diazadiphosphetidine 4. In solution, these compounds are in equilibrium, presumably involving the not detectable iminophosphorane 2. A single X-ray analysis carried out on 3 proves the structure of this type of compound which has been postulated earlier as intermediate in the synthesis of aziridines from azidoalcohols^1,2     

Phendione in the Synthesis of Annelated Derivatives of 4,7-Phenanthroline

By condensation of 5-phenyl-1,3-cyclohexanedione with 6-quinolylamine and aldehydes of aromatic, heterocyclic, and cyclohexene series new 12-aryl(heteryl, cyclohexenyl)-9-phenyl-8,9,10,12-tetrahydro-7H-benzo[b][4,7]phenanthrolin-11-ones were prepared. The presence of diastereomers in the target reaction products was determined by ¹H NMR spectroscopy.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 5, 2005, pp. 742–748.Original Russian Text Copyright © 2005 by Gusak, Tereshko, Kozlov.     

A General Method for the Synthesis of 11-Deoxyanthracyclinones

A general method for the synthesis of 11-deoxyanthracyclinones is described.     

Synthesis and Reactions of Haloazodienes. A New and General Synthesis of Substituted Pyridazines

The reaction of dihalohydrazones with Hünig's base gives 1-carbethoxy-3-phenyl-4-haloazodienes in-situ, which were found to combine with a variety of electron rich olefins to yield halo-substituted tetrahydropyridazines (Scheme 2 and Table 1 ). These haloazodiene cyclizations are best characterized as inverse electron demand, 4 + 2 hetero Diels-Alder reactions that maintain a high degree of regio- and stereochemical control (Schemes 5 and 6). The chloro-substituted tetrahydropyridazines that are formed give high yields of substituted pyridazines upon treatment with base (Table 1). The sequence of a chloroazodiene cyclization to a tetrahydropyridazine followed by an aromatization constitutes a new and general synthesis of substituted pyridazines. In contrast to the haloazodiene cyclizations, the novel cyclization reactions of the in-situ generated 1-carbethoxy-3-phenyl-4,4-dichloroazodiene were found to give N-aminopyrroles and pyridazines when combined with acyclic enamines (Table 3 ). However, reactions with cyclic enamines gave the N-aminopyrroles, pyridazines, a dihydropyridazine as products as well as the noncyclized enamine intermediates (Table 4 ). The noncyclized enamines could be converted to the N-aminopyrroles simply upon heating to higher temperatures, indicating a stepwise mechanism (Schemes 8 and 9). The examples described here are the first reported cyclization reactions for dichloroazodienes.     

Novel Variant of the Tricyclooctanone Approach to Cyclopentanoid Natural Products. Synthesis of (±)-Coriolin. Preliminary Communication

A total synthesis of the antitumor sesquiterpene coriolin ( 9 ; racemic) in 11 steps from 3,3,6-trimethylbicyclo[2.2.2]oct-7-ene-2,5-dione ( 2a / 2b ) is described (yield 2a / 2b → 8: 28%). The sequence is unprecedentedly short and avoids difficult separation problems. The key step in the scheme is a novel facet of oxadi-π-methane photochemistry, i.e., the steering by subtle steric effects of the β,γ-unsaturated ?-diketone to undergo a regioselective photorearrangement involving one β,γ-enone partial chromophore. Furthermore, the overall phototransformation, which can be carried out at unusually high concentrations (≥20% solutions), involves also a Norrish type I process equilibrating the two epimeric starting enediones 2a and 2b in favour of the desired stereoisomer.     

A General Method for the Vinylation of Nitrones. Synthesis of Allyl Hydroxylamines and Allyl Amines

An examination of the vinylation of several nitrones is presented. Whereas a complete diastereofacial discrimination was observed upon the addition of vinyl organometallic reagents to α-alkoxy nitrones, the same reaction with α-amino nitrones gave syn adducts in all cases, with the only exception of a L-serine-derived α-amino monoprotected nitrone. The obtained allyl hydroxylamines were easily transformed into synthetically valuable allyl amines.     

A General Method for the Synthesis of N,N-Dialkylaminobutylamines

A general method for the synthesis of N,N-dialkylaminobutylamines 4 from readily available chloroacetamides 6 is described.     

Synthesis of Formyl Derivatives of 2-Hetarylimidazoles Annelated with Naphthalene and Phenanthrene Rings

The formylation reaction of a series of 2-hetarylimidazoles, annelated by naphthalene and phenanthrene rings, using hexamethylenetetramine in PPA and the Vilsmeier reagent has been studied. The furyl and thienyl derivatives form principally the 5-formyl-substituted and the pyrrolylimidazoles were found to give a mixture of the - and -formyl derivatives.