Nadia R. Mohamed

Synthesis and biological evaluation of some nitrogen containing steroidal heterocycles

epi-Androsterone 1 was converted into its hydrazone derivative through the reaction with hydrazine hydrate 80%. Hydrazonoandrostane derivative 2b reacted with hydrazonoyl halides in the presence of K(2)CO(3) forming the corresponding hydrazopyridazinoandrostane derivatives 6a-d. The 3β-acetyl-17-hydrazonoandrostane derivative 2b reacted with a halogen reagent, benzoyl chloride, to form the non-cyclic 16-benzoylated hydrazone 9. On the other hand, compound 2b produced the corresponding pyridazinoandrostane derivatives 11 and 12 via its reaction with phenacyl bromide and chloroacetone respectively. Reaction of the hydrazono derivative 2b with benzaldehyde in the presence of acetic acid drops led to the formation of the benzylidenehydrazonoandrostane derivative 13. The product 14, phosphinom-ethylenehydrazonoandrostane was obtained by the reaction of the derivative 13 with trisdimethylaminophosphine in the presence of dry benzene. The reaction of compound 2b with phenyl isothiocyanate followed by boiling in chloroacetic acid or thioglycolic acid produced the pyrazoloandrostane derivatives 17 and 18 respectively. The biological activity of compounds 6a, 6d, 11, 12, and 15 was evaluated as inhibitor of growth in a human liver carcinoma cell line and doxorubicine was used for comparison. Compounds 15 and 12 showed a higher potency than the other tested compounds.

Studies on Organophosphorus Compounds VII1,2: Transformation of Steroidal Ketones with Lawesson's Reagent into Thioxo and Heterofused Steroids. Results of Antimicrobial and Antifungal Activity

The reactivity of Lawessons reagent (LR) toward some steroidal hormones was studied, 4-androsten-3,17-dione 2 reacted with LR to produce the corresponding thioxosteroids 3 and 4. Epi-androsterone 5 showed a great activity to LR and produced 3β-mercaptospiro-(androstan-17,4′dithiaphosphetan)thione 8 and the sulfide derivative 9. Also progesterone 10 reacted with LR to yield the thiaphospholo[3′, 4′:16,17]androsten-3-one 13 and the sulfide product 16. The new modified steroidal derivatives thieno[2′,3′:2,3]cholestan 18 and thieno[2′,3′:2,3]-androstan 20 were synthesized and examined against LR, the corresponding thiazaphosphorinothieno steroidal derivatives 23 and 24 were isolated respectively. The in vitro biological activity of some newly synthesized compounds against bacteria, yeast, and fungi was studied.

Studies on Organophosphorus Compounds XI: The Reaction of Phosphorus Reagents With Hydrazonoyl Halides, Hydrazonoyl Azides, and Shiff's Bases

N-(chloro-furan-2-yl)methylene-N′-(4-nitrophenyl)hydrazone (I) reacted with triethylphosphite to produce the phosphonate derivative III. The tetrazine derivative VI was produced by the interaction of I with diethyl-phosphite. Hydrazonoyl azide derivatives VIIIa–c reacted with triphenyl phosphine to form the iminophosphorane derivatives Xa–c. On the other hand, the azide derivative VIIIc reacted with the phosphonium ylide XI to form the 1,2,3-triazole adduct XIII. The reaction of triethyl phosphite with Shiffs bases XIVa–c yielded the corresponding phosphonates XVa–c. The structures of the newly prepared compounds were confirmed with the analytical and spectroscopic evidences. *C.f. Reference 20.

A novel synthesis of phosphorus heterocycles. Reaction of α-hydrazidoyl halides with phosphoranes and Lawesson's reagent

Hydrazidoyl halides 1a reacted with diethylphosphonoacetonitrile (2a) in sodium ethoxide to yield the hydrazine derivative 4a which readily cyclized to form the corresponding diazaphosphole 5 . The latter was hydrolyzed to form the final product 6, with the formation of a low yield of a second product 7a . Similarly 1b, c reacted with diethylphosphonoacetonitrile and triethylphosphonoacetate 2a, b to produce the corresponding diazaphospholes 6b–d . Interaction of hydrazidoyl halides 1b, d–g with Lawessons reagent in dry toluene produced 1,3,4-thiadiazaphosphole derivatives 10b, d, e and 11f, g respectively.

STUDIES ON ORGANOPHOSPHORUS COMPOUNDS V1-4. REACTION OF 2,4-BIS(4-METHOXYPHENYL)-1,3,2,4-DITHIA DIPHOSPHETANE-2,4-DISULFIDE WITH CYCLIC AND HETEROCYCLIC KETONES

Abstract Cyclic ketones 2 and 8a,b reacted with Lawessons reagent (1) in different molar ratios to give the oxathiaphosphole (4). the disulfide 7 and the dithiones 9a,b. N-Methyl barbituric acid (10b) reacted with LR to produce the enethiole 11 and the sulfide 12. Pyrazolone derivatives 13 and 17 reacted with LR in different molar ratios to form the corresponding products 15,16 and 19. Rohdanine (20) reacted with LR to give the enethiole 22 and the disulfide 23.

STUDIES ON ORGANOPHOSPHORUS COMPOUNDS VI1–5: Utility of Lawesson's Reagent for Synthesis of Thiaphosphorine, Thioxanthene, and Thiaphosphole Derivatives

Arylidene malonate derivatives 2a–c reacted with Lawessons reagent (1) LR in equimolar ratio to yield the oxathiaphosphorine derivatives 3a–c. The behaviour of LR towards cyclic ketones was also examined and yielded the thioxanthene derivatives 5a,b. On the other hand, arylidene pyrazolone 8 reacted with LR to give the phosphole 10. Aminobenzenethiophene 11 reacted with LR under reflux to produce the corresponding thiazaphosphorine 12.

Phosphonium Ylides In Organic Synthesis III. 12 A Novel Synthesis Of α-Substituted Ylides and Pyrazole Systems

Abstract A novel synthesis of a-substituted phosphonium ylides and pyrazole systems via the treatment of hydrazonoyl halides 1 with phosphoranes 2 and 6, respectively is reported.

Heterocyclic Sulfonesiv: A Novel Synthesis of Pyrrole and Fused Heterocyclic Sulfones

Abstract The applicability and synthetic potency of the reagent diethyl 2-aryl-3-phenylsulfonylpropen-l,1-dicarboxylate 3 is reported. Compound 3 proved to be a key precursor in heterocyclic sulfones synthesis. Chemical and spectroscopic evidences for the structure of the newly synthesized compounds are described.

Heterocyclic Synthesis with Activated Nitriles: An Expeditious Synthetic Approach to Polyfunctionally Substituted Pyrroles, Heterocyclopyrimidines and Coumarins

Abstract The applicability and synthetic potency of the new reagent N-(2,2-dicyanoethenyl)aminoacetonitrile (3) to develop an expeditious convenient synthetic route of unique polyfunctionally substituted pyrroles, heterocyclopyrimidines, and 2H-1-benzopyran-2-ones is reported. Chemical and spectroscopic evidence for the structures of the newly synthesized compounds are described.

REACTION OF PHOSPHORANES WITH CINNAMONITRILES. A NOVEL SYNTHESIS OF α-SUBSTITUTED PHOSPHONIUM YLIDES

Abstract Reaction of phosphoranes with cinnamonitriles. Synthesis of α-substituted-β-arylacrylic acids via the Witting reaction.