ChemInform Abstract: HETEROCYCLIC ANALOGS OF STEROIDS. V. SYNTHESIS AND SOME PROPERTIES OF 8‐AZA‐16‐OXAGONANE‐12,17‐DIONE DERIVATIVES

Abstract

Säurekatalysierte Kondensationen der Dihydroisochinoline (I) mit der Tetronsäure (II) in siedendem Toluol (azeotrope Wasserabscheidung) liefern die Steroid‐Analogen (III), daneben auch geringe Mengen ihrer Dehydrierungsprodukte (IV); (IIIb) fällt als Gemisch der 15α‐ und 15β‐Isomeren an (1H‐NMR‐Spektren).

Cyclic azomethines and their hydrogenated derivatives. (Review)

“…In the majority of studies on the synthesis of 8-azasteroids using cyclic azomethines the reaction scheme was analogous to that shown, usually the carbonyl components were modified [257][258][259][260][261][262][263][264][265][266][267][268][269][270][271]. An important achievement of the authors of these studies is the demonstration of the stereochemistry of the azasteroids obtained and their derivatives.…”

Mechanism for annelation ([2+4] cyclocondensation) of Schiff bases by β-dicarbonyl and β,β′-tricarbonyl compounds in amphiprotic media (review)

“…It is known that and became a stimulus and a basis of development of an alternative mehanism the reactions of 2-acyl-1,3-cyclopentanediones with 3,4-dihydroisoquinolines not substituted at C-1 lead to annelation products 9 (X = CH 2 ), while the reactions with 3-acetyltetronic, 3-acetyltetramic, and 3-acetylthiotetronic acids give annelation products 11 (X = N, O, S) only in protic media, excluding the formation of β,β'-triCC amions 4A (4)(5)(6)8]. On the other hand, all attempts to achieve condensation of 1-Alk-3,4-dihydroisoquinolines with β,β'-triCC containing five-membered cyclic fragments were unsuccessful.…”

“…They sought to relate these findings to differences in the acid-base properties of β-diCC and β,β'-triCC and competition between the acid-base properties of the medium and of the reagents [1]. A similar approach was adopted by subsequent workers who studied this reaction [4][5][6].…”

“…In subsequent investigations, which expanded the scope of this reaction to other β-diCC, β,β'-triCC, and azomethines and demonstrated the considerable synthetic potential of this reaction for the one-stage preparation of various AH [2,[4][5][6][7], additional information was obtained relevant to improving the reaction conditions. New questions arose concerning the steps and intermediates as well as even the reaction sequence 1 + 2 → 4 → 5 → 6 → 3 on the whole.…”

“…In particular, the introduction of alkyl(methyl, ethyl, or isopropyl) substituents into position 1 in the 3,4-dihydroisoquinolines or replacement of the acetyl substituent in the β,β'-triCC by a propanoyl, butanoyl, or isobutanoyl substituent has no significant effect on the reaction rate or the product yields [2,7]; -the reaction does not proceed with 3-substituted 3,4-dihydroisoquinoline derivatives (3-Me or 3-CO 2 Me) [2,7]; -the condensation with 5-substituted (5-Me, 5-Ph), asymmetrical 4-substituted (4-Me, 4-CO 2 Me, 4-Cl, 4-Br, 4-OAc), and optically-active ((+)-4(R)-and ((-)-4(S)-OH) 2-acyl-1,3-cyclohexanediones proceeds regio-and stereoselectively to give isoquino[2,1-a]quinolines (dibenzo[a,f]quinolizines or 8-aza-D-homogonanes) 7-10a,b (R = H, OMe; R 1 = H, Me, Et, i-Pr; R 2 = Me, Ph; R 3 = Me, CO 2 Me Cl., Br; Z = CH 2 , CMe 2 , Scheme 2) [2,7,10]; -while heating is necessary for the cyclodehydration 5 → 6 → 3 (Scheme 1) [1, [4][5][6], the condensation with 2-acyl-1,3-cyclohexanediones containing normal acyl(propanoyl, butanoyl) substituents also occurs without heating [2,7]; -the reaction rate was found to depend on the reagent concentrations and the reaction stops in the concentration range from 2.5·10 -2 to 7.5·10 -3 mol/liter; -condensation occurs with β,β'-triCC with five-membered heterocyclic fragments (3-acetyltetronic, 3-acetyltetramic, and 3-acylthiotetronic acids) only in protic media such as acetic acid, trifluoroacetic acid, and AlkOH·HCl [5,6]. Syntheses were reported in these studies for 12,12-dimethylisoquino[2,1-a]quinolines 7 and angularly alkylated derivatives 8-10 [2], cis-diastereomeric 3,11b-derivatives of isoquino[2,1-a]quinolines 8 (represented by the α,α-diastereomer, Scheme 2), diastereomeric 2,11b,12-derivatives of isoquino[2,1-a]quinolines 9 [2,7], and enantiomeric (-)-(4R,11bR)-and (+)-(4S,11bS)-hydroxy derivatives of isoquino[2,1-a]quinolines (15-hydroxy-8-aza-D-homogona-12,17a-diones) 10a and 10b [10], and diheteroatomic derivatives 11 (X = O, N, S) [5,6,8]. These results are also evidence against the mechanism given in Scheme 1, in particular, since the hypothetic Michael addition C,C adducts with ketimine azomethines (1-Alk-3,4-dihydroisoquinolines) etc.…”