Pentacyclic Ring System Research Articles

Total synthesis of (-)- and ent-(+)-vindoline.

[reaction: see text] Two exceptionally concise total syntheses of (-)- and ent-(+)-vindoline are detailed enlisting a diastereoselective tandem [4 + 2]/[3 + 2] cycloaddition of a 1,3,4-oxadiazole. The unique reaction cascade assembles the fully functionalized pentacyclic ring system of vindoline in a single step that forms four C-C bonds and three rings while introducing all requisite functionality and setting all six stereocenters within the central ring including three contiguous and four total quaternary centers.

Azinyl sulfides. LXXXI. 14-Phenyl-7-thiapyrano[2,3-c;6,5-c′]diquinoline-14-carbonitrile

The molecules of the title compound, C26H15N3S, have a pentacyclic ring system which is almost planar, with the central ring in a flattened boat conformation. The folding angle between the two quinoline rings is 6.75 (7) degrees. The 14-phenyl substituent is in a quasi-axial conformation, while the 14-cyano substituent is in a quasi-equatorial conformation with respect to the thiopyran ring. The S...C-C(phenyl) and S...C-C(CN) angles are 116.8 (2) and 129.3 (2) degrees, respectively. The plane of the phenyl group is nearly coplanar with the plane bisecting the dihedral angle of the pentacyclic ring system.

Naucleamides A—E, New Monoterpene Indole Alkaloids from Nauclea latifolia.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Naucleamides A-E, new monoterpene indole alkaloids from Nauclea latifolia.

Five new monoterpene indole alkaloids, naucleamides A-E (1-5), were isolated from the bark and wood of Nauclea latifolia, and the structures and relative stereochemistry were elucidated from the spectroscopic data. Naucleamide E (5) is a unique monoterpene indole alkaloid possessing a pentacyclic ring system with an amino acetal bridge.

Synthesis and Reactions of Benzotriazolyl‐Substituted Spiro[cyclohexane‐1,2′‐2′H‐imidazo[4,5‐b]pyridine

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and Reactions of Benzotriazolyl-Substituted Spiro[Cyclohexane-1,2′-2′H-Imidazo[4,5-b]Pyridine

The introduction of N and S-nucleophiles into the 2H-4-azabenzimidazole system using the 1H-benzotriazole ring as a synthetic auxiliary, and also the syntheses of novel pentacyclic ring systems by application of the Graebe-Ullmann method, are described.

X-ray structure of 6-phenyldiquino[3,2-b;5,6-b′] [1,4]thiazine

The title compound (C24H15N3S) is monoclinic, with a = 10.816(1), b = 8.193(1), c = 10.892(1), β = 104.20(1)° and space group P21. The molecule is folded with the central ring in a boat conformation. It can also be considered as folded around the C—C axis between the thiazine and pyridine rings. The butterfly folding angle between the two quinoline planes is 20.5(1)° and between the planes of the two halves of the thiazine ring is 30.6(1)°. The phenyl substituent is in an equatorial location with respect to the thiazine ring with the C—N···S angle of 163.0(2)°. The phenyl plane nearly bisects the pentacyclic ring system and is nearly perpendicular to the C(2), C(3), C(12), C(13) plane.

Progress towards viridin: synthesis of the pentacyclic furanosteroid ring system via o-benzoquinonoid cycloadditions

The pentacyclic ring system of viridin is synthesised in nine steps from 4-methylguaicol by means of successive cycloadditions involving o-benzoquinonoid intermediates generated in situ.

ChemInform Abstract: Asymmetric Synthesis of the Pentacyclic Ring System of Aspidosperma Alkaloids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Saturated heterocycles. 254. synthesis and stereochemistry of saturated or partially saturated pyridazino‐[6,1‐b]‐ and phthalazino[1,2‐b]quinazolinones

AbstractBy the reaction of anthranilic hydrazide 1 with cis‐2‐(p‐methylbenzoyl)‐1‐cyclohexanecarboxylic acid 2a or diendo‐3‐(p‐methylbenzoyl)bicyclo[2.2.1]heptane‐2‐carboxylic acid 2b, fused tetra‐ and pentacyclic ring systems 3a, b were prepared, trans‐2‐Amino‐1‐cyclohexanecar‐bohydrazide 4b was reacted with 3‐(p‐chlorobenzoyl)propionic acid 5 to yield the pyridazino[6,1‐b]quinazolinone 6. From the reaction of cis‐2‐amino‐1‐cyclohexanecarbohydrazide 4a with 2a, three isomeric partially saturated 8H‐phthalazino[1,2‐b]quinazolin‐8‐ones 7a‐c were formed. The reaction of diexo‐2‐aminobicyclo[2.2.1]heptane‐3‐carbohydrazide 4c and 2a furnished the pentacyclic derivatives 8 and 9 containing a 3‐aryl‐4,5‐dihydropyridazine or 3‐arylhexahydropyridazine ring C with cis annelated C/D rings. The formation of 8 and 9 involving different ring systems can be rationalized by two reaction pathways: (i) in the bislactam 9 the carboxyl group acylates the hydrazide, while (ii) in 8 it forms a pyridazine ring with the cyclic amino group by cyclocondensation. The structures of the products were elucidated by 1H and 13C nmr methods, including DEPT, DNOE and 2D‐HSC measurements.

Asymmetric synthesis of the pentacyclic ring system of Aspidosperma alkaloids

The asymmetric synthesis of pentacyclic compound 13, a known intermediate in the synthesis of l-acetylaspidospermidine, was conducted via the condensation of 2-hydroxytryptamine with chiral C9 lactone 9, readily available from triol 4.

Total Syntheses of Lamellarin D and H. The First Synthesis of Lamellarin-Class Marine Alkaloids

Total syntheses of marine polyaromatic alkaloids, lamellarin D (1) and H (2), are described. The pentacyclic lamellarin ring system was constructed by N-ylide mediated pyrrole ring formation and subsequent lactonization of 4 obtained by an assembly of known benzylisoquinoline 5, benzoate 6 and ethyl bromoacetate. © 1997 Elsevier Science Ltd.

An Approach to the Synthesis of the Manzamine Alkaloids Via the Vinylogous Amide PHotocycloAddition/Retro‐Mannich Fragmentation/Mannich Closure Cascade (pharM)

AbstractThe application of the vinylogous amide [2+2] photocycloaddition/retro‐Mannich fragmentation/Mannich closure cascade (pharM) to the synthesis of the pentacyclic ring system of the anti‐leukemic marine alkaloid manzamine A is presented. Two approaches to the synthesis of the requisite pentacycle are described: (a) the transannular photocycloaddition of an 18‐membered vinylogous amide; and (b) photocycloaddition of an acyclic vinylogous amide, followed by macrolactamization of the derived pharM closure product to generate the pentacyclic ring system.

ChemInform Abstract: Construction of the Pentacyclic Ring System of Apogeissoschizine.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of the antitumor antibiotic FR-66979: Dmitrienko oxidative expansion of a fully functional core structure

A stereocontrolled synthesis of the pentacyclic ring system 18, a projected advanced intermediate in the synthesis of FR-66979 ( 2), has been achieved. Key steps in the assembly of 18 include a copper(I) mediated cylization-oxidation of diazoketone 6 to mitosene 16 followed by an oxidative expansion of 16 to 18. The latter transformation proceeds via N-oxidation of diol 17.

Construction of the pentacyclic ring system of apogeissoschizine

The synthesis of pentacyclic apogeissoschizine-type compounds is reported. It involves the construction of the seven-membered E ring by addition of the enolate derived from methyl 1-indolepropionate to the γ-position of a pyridinium salt, with subsequent acid-promoted cyclization of the resulting 1,4-dihydropyridine, and the closure of the C ring by cyclization on the indole 3-position in the last synthetic step.

Acetyl-11-keto-beta-boswellic acid (AKBA): structure requirements for binding and 5-lipoxygenase inhibitory activity.

1. 5-Lipoxygenase (5-LOX) products from endogenous arachidonic acid in ionophore-stimulated peritoneal polymorphonuclear leukocytes (PMNL) and from exogenous substrate (20 microM) in 105,000 g supernatants were measured. 2. The effects of natural pentacyclic triterpenes and their derivatives on 5-LOX activity were compared with the inhibitory action of acetyl-11-keto-beta-boswellic acid (AKBA), which has been previously shown to inhibit the 5-LOX by a selective, enzyme-directed, non-redox and non-competitive mechanism. 3. The 5-LOX inhibitory potency of AKBA was only slightly diminished by deacetylation of the acetoxy group or reduction of the carboxyl function to alcohol in intact cells (IC50 = 1.5 vs. 3 and 4.5 microM, respectively) and in the cell-free system (8 vs. 20 and 45 microM). 4. beta-Boswellic acid (beta-BA), lacking the 11-keto function, inhibited 5-LOX only partially and incompletely, whereas the corresponding alcohol from beta-BA, as well as amyrin, acetyl-11-keto-amyrin, 11-keto-beta-boswellic acid methyl ester had no 5-LOX inhibitory activity up to 50 microM in either system. 5. beta-BA only partially prevented the AKBA-induced 5-LOX inhibition, whereas the non-inhibitory compounds, amyrin and acetyl-11-keto-amyrin, almost totally antagonized the AKBA effect and shifted the concentration-inhibition curve for the incomplete inhibitor beta-BA to the right. In contrast, the non-inhibitory 11-keto-beta-BA methyl ester exerted no antagonizing effect. 6. The results demonstrate that the pentacyclic triterpene ring system is crucial for binding to the highly selective effector site, whereas functional groups (especially the 11-keto function in addition to a hydrophilic group on C4 of ring A) are essential for 5-LOX inhibitory activity.

The chemistry of the taxane diterpene: Stereoselective synthesis of 10-deacetoxy-11,12-epoxypaclitaxel

Epoxidation of the olefin in 10-deacetoxybaccatin III ( 6) and 10-deacetoxypaclitaxel ( 9) was accomplished with meta-chloroperbenzoic acid leading to a novel pentacyclic ring system. Hydroxyl directed delivery of the epoxidizing agent did not appear to play a role in the stereoselectivity of the reaction as epoxidation occurred at the β-face of the molecule. 10-Deacetoxy-11,12-epoxypaclitaxel ( 10) proved to be more active than paclitaxel ( 1) in the microtubule assembly assay and three-fold less cytotoxic than paclitaxel against B16 melanoma cells.

Acetyl Coenzyme A:Salutaridinol-7-O-Acetyltransferase from Papaver somniferum Plant Cell Cultures:: THE ENZYME CATALYZING THE FORMATION OF THEBAINE IN MORPHINE BIOSYNTHESIS

Acetyl coenzyme A:salutaridinol-7-O-acetyltransferase, a highly substrate-specific enzyme, has been purified nearly 3,000-fold to homogeneity from Papaver somniferum plant cell suspension cultures. Purification was achieved by fractionated ammonium sulfate precipitation, dye-ligand affinity chromatography on matrex red A, gel filtration, ion exchange chromatography on Mono Q and a second dye-ligand affinity chromatography on fractogel TSK AF Blue. The purified enzyme was a single polypeptide with an M(r) = 50,000 displaying an isoelectric point of 4.8, a pH optimum between pH 6 and 9 and a temperature optimum at 47 degrees C. The Km values for the substrate salutaridinol and the co-substrate acetyl co-enzyme A were 7 and 46 microM, respectively. Salutaridinol-7-O-acetyltransferase catalyzes the stoichiometric transfer of the acetyl group from acetyl coenzyme A to the 7-OH group of salutaridinol yielding salutaridinol-7-O-acetate, which is a new intermediate in morphine biosynthesis. Salutaridinol-7-O-acetate undergoes a subsequent spontaneous allylic elimination at pH 8-9, leading to the formation of thebaine (1), the first morphinan alkaloid with the complete pentacyclic ring system, or at pH 7 leading to dibenz[d,f]azonine alkaloids that contain a nine-membered ring. Acetylation and subsequent allylic elimination is a new enzymic mechanism in alkaloid biosynthesis, which in the poppy plant can transform one precursor into alkaloids possessing markedly different ring systems, depending on the reaction pH.

Synthesis of 4‐Aminopyrimidines from 1,2,4‐Oxadiazoles, V[1]. Reductive Formation of 2‐(Benzoylamino)indole from 3‐(2‐Aminobenzyl)‐5‐phenyl‐1,2,4‐oxadiazole and Its Transformation to 6‐Phenyl‐8H‐pyrimido‐[1,6‐a: 4,5‐b']diindole, a New Heterocyclic Ring System

AbstractCatalytic hydrogenation of 5‐substituted 3‐(2‐aminobenzyl)‐1,2,4‐oxadiazoles 7 give 2‐(acylamino)indoles 10. Treatment of 2‐(benzoylamino)indoles 10a–c with acid leads to the novel 6‐phenyl‐8H‐pyrimido[1,6‐a: 4,5‐b']diindoles 19a–c. A route for the new ring formation is proposed. Catalytic hydrogenation of 19a (Raney nickel, 70°C, atmospheric pressure) saturates the 6‐phenyl ring but leaves the pentacyclic ring system intact. The structure of 19a is confirmed by an X‐ray crystallographic analysis.