Synthetic studies of zoanthamine alkaloids. Stereoselective synthesis of the ABC ring system of norzoanthamine by an intramolecular Diels–Alder reaction

The zoanthamine alkaloids, a type of heptacyclic marine alkaloid isolated from colonial zoanthids of the genus Zoanthus sp., have distinctive biological and pharmacological properties as well as their unique chemical structures with stereochemical complexity. Namely, norzoanthamine can suppress the loss of bone weight and strength in ovariectomized mice and has been considered a promising candidate for an antiosteoporotic drug, whereas zoanthamine has exhibited potent inhibitory activity toward phorbol myristate-induced inflammation in addition to powerful analgesic effects. Recently, norzoanthamine derivatives were demonstrated to inhibit strongly the growth of P-388 murine leukemia cell lines, in addition to their potent antiplatelet activities on human platelet aggregation. These distinctive biological properties, combined with novel chemical structures, make this family of alkaloids extremely attractive targets for chemical synthesis. However, the chemical synthesis of the zoanthamine alkaloids has been impeded owing to their densely fuctionalized complex stereostructures. We report here the first and highly stereoselective total syntheses of norzoanthamine and zoanthamine, which involves stereoselective synthesis of the requisite triene for intramolecular Diels-Alder reaction via three-component coupling reactions, a key intramolecular Diels-Alder reaction, and subsequent crucial bis-aminoacetalization as the key steps.

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ChemInform Abstract: An Intramolecular Diels-Alder Reaction Involving Fulvenes as 4π Components - Stereoselective Synthesis of Novel Oxatricyclo[6.4.0.02,10]dodeca-2,11-diene Ring System.

ChemInform ◽

10.1002/chin.200226171 ◽

2010 ◽

Vol 33 (26) ◽

pp. no-no

Author(s):

S. Manikandan ◽

M. Shanmugasundaram ◽

R. Raghunathan

Keyword(s):

Stereoselective Synthesis ◽

Alder Reaction ◽

Ring System ◽

Diels Alder ◽

Diels Alder Reaction

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ChemInform Abstract: Chiral Holmium Complex-Catalyzed Diels-Alder Reaction of Silyloxyvinylindoles: Stereoselective Synthesis of Hydrocarbazoles.

ChemInform ◽

10.1002/chin.201412148 ◽

2014 ◽

Vol 45 (12) ◽

pp. no-no

Author(s):

Shinji Harada ◽

Takahiro Morikawa ◽

Atsushi Nishida

Keyword(s):

Stereoselective Synthesis ◽

Alder Reaction ◽

Diels Alder ◽

Diels Alder Reaction

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Crystal structures and conformations of two Diels–Alder adduct derivatives: 1,8-bis(thiophen-2-yl)-14-oxatetracyclo[6.5.1.02,7.09,13]tetradeca-2(7),3,5-trien-10-one and 1,8-diphenyl-14-oxatetracyclo[6.5.1.02,7.09,13] tetradeca-2,4,6-trien-10-one

Acta Crystallographica Section E Crystallographic Communications ◽

10.1107/s2056989015001073 ◽

2015 ◽

Vol 71 (2) ◽

pp. 213-216

Author(s):

S. Gopinath ◽

P. Narayanan ◽

K. Sethusankar ◽

Meganathan Nandakumar ◽

Arasambattu K. Mohanakrishnan

Keyword(s):

Crystal Packing ◽

Rotation Axis ◽

Alder Reaction ◽

Ring System ◽

Diels Alder ◽

Compound I ◽

Diels Alder Reaction ◽

Phenyl Rings ◽

Axis Parallel ◽

Alder Adduct

The title compounds, C21H16O2S2(I) and C25H20O2(II), are products of a tandem `pincer' Diels–Alder reaction consisting of [2 + 2] cycloadditions between benzo[c]furan and cyclopentanone. Each comprises a fused tetracyclic ring system containing two five-membered rings (inenvelopeconformations with the O atom as the flap) and six-membered rings (inboatconformations). In addition, two thiophene rings in (I) and two phenyl rings in (II) are attached to the tetracyclic ring system. The cyclopentanone ring adopts atwistedconformation in (I) and anenvelopeconformation in (II). In (I), the thiophene rings are positionally disordered over two sets of sites, with occupancy ratios of 0.901 (2):0.099 (2) and 0.666 (2):0.334 (2). In (II), the oxygen atom of the cyclopentanone ring is rotationally disordered over two sites with an occupancy ratio of 0.579 (4):0.421 (4). The molecular structure of (I) is stabilized by an intramolecular C—H...O hydrogen bond, which generates anS(7) ring motif. In the crystal, the molecules are linkedviaweak C—H...O hydrogen bonds, which generateR22(16) ring motifs in (I) andC(8) chains in (II). In both structures, the crystal packing also features C—H...π interactions. The crystal studied of compound (I) was twinned by non-merohedry. The twin component is related by the twin law [−1 0 0 −0.101 1 −0.484 0 0 −1] operated by a twofold rotation axis parallel to thebaxis. The structure of (I) was refined with a twin scale factor of 0.275 (2).

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