Phthalides and Phthalans: Synthetic Methodologies and Their Applications in the Total Synthesis

Chemistry remains an experimental science. The theory of chemical bonding leaves much to be desired. Yet, the past 20 years have been marked by a fruitful symbiosis of organic chemistry and molecular orbital theory. Of necessity this has been a marriage of poor theory with good experiment. Tentative conclusions have been arrived a t on the basis of theories which were such a patchwork on approximations that they appeared to have no right to work; yet, in the hands of clever experimentalists, these ideas were transformed into novel molecules with unusual properties. In the same way, by utilizing the most simple but fundamental concepts of molecular orbital theory we have in the past 3 years been able to rationalize and predict the stereochemical course of virtually every concerted organic reaction.' In our work we have relied on the most basic ideas of molecular orbital theory-the concepts of symmetry, overlap, interaction, bonding, and the nodal structure of wave functions. The lack of numbers in our discussion is not a weakness-it is its greatest strength. Precise numerical values would have to result from some specific sequence of approximations. But an argument from first principles or symmetry, of necessity qualitative, is in fact much stronger than the deceptively authoritative numerical result. For, if the simple argument is true, then any approximate method, as well as the now inaccessible exact solution, must obey it. The simplest description of the electronic structure of a stable molecule is that i t is characterized by a finite band of doubly occupied electronic levels, called bonding orbitals, separated by a gap from a corresponding band of unoccupied, antiboding levels as well as a continuum of higher levels. The magnitude of the gap may range from 40 kcal/mole for highly delocalized, large aromatic systems to 250 kcal/mole for saturated hydrocarbons. It should be noted in context that socalled nonbonding electrons of heteroatoms are in fact bonding. Consider a simple reaction of two molecules to give a third species, proceeding in a nonconcerted manner through a diradical intermediate I. A + B + [I] + C

The Conservation of Orbital Symmetry (福井謙一とフロンティア軌導理論) -- (参考論文)

A Convenient Method for Synthesizing 2-Aryl-3-hydroxy-4-oxo-4H-1-benzopyrans or Flavonols

Recent investigations show that naturally occurring biflavanoids possess anti-inflammatory, anticancer, antiviral, antimicrobial, vasorelaxant, and anticlotting activities. These activities have been discovered from the small number of biflavanoid structures that have been investigated, although the natural biflavanoid library is likely to be large. Structurally, biflavanoids are polyphenolic molecules comprised of two identical or non-identical flavanoid units conjoined in a symmetrical or unsymmetrical manner through an alkyl or an alkoxy-based linker of varying length. These possibilities introduce significant structural variation in biflavanoids, which is further amplified by the positions of functional groups--hydroxy, methoxy, keto, or double bond--and stereogenic centers on the flavanoid scaffold. In combination, the class of biflavanoids represents a library of structurally diverse molecules, which remains to be fully exploited. Since the time of their discovery, several chemical approaches utilizing coupling and rearrangement strategies have been developed to synthesize biflavanoids. This review compiles these synthetic approaches into nine different methods including Ullmann coupling of halogenated flavones, biphenyl-based construction of biflavanoids, metal-catalyzed cross-coupling of flavones, Wessely-Moser rearrangements, oxidative coupling of flavones, Ullmann condensation with nucleophiles, nucleophilic substitutions for alkoxy biflavanoids, and dehydrogenation-based or hydrogenation-based synthesis. Newer, more robust synthetic approaches are necessary to realize the full potential of the structurally diverse class of biflavanoids.

Synthesis of Biologically Relevant Biflavanoids – A Review

A direct efficient diastereoselective synthesis of enantiopure 3-substituted-isobenzofuranones

Novel series of pyrazolo[3,4-b]pyridines with basic skeleton different from the known COX inhibitors were synthesized from 5-amino-1-[4-(aminosulfonyl)phenyl]-3-phenyl-1H-pyrazole, which in turn was prepared by the condensation of (4-sulfamoylphenyl)hydrazine with α-cyanoacetophenone. All the newly synthesized compounds were tested for their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema assay. Some of the most potent compounds were evaluated in different COX and LOX assays. Some of the new compounds were found to possess moderate anti-inflammatory activity.

Synthesis and anti-inflammatory evaluation of some pyrazolo[3,4- b ]pyridines

Vilsmeier–Haack reaction has been found to be an excellent method for the formylation of a variety of hydrazones to yield the corresponding 4-formylpyrazoles.

Vilsmeier–Haack Reaction on Hydrazones: A Convenient Synthesis of 4-formylpyrazoles:

Photoirradiation of 3-alkoxy-6-chloro-2-(2′-furyl)-4-oxo-4H-1-benzopyrans 3 led to the formation of methyl 8-chloro-10-oxo-2-phenyl-2,3,4,10-tetrahydropyrano[3,2-b][1]benzopyran-3-ylacetate 4. The reaction proceeds through the formation of 8-chloro-4-phenyl-3a,4,6,11b-tetrahydrofuro-[2′,3′:4,5]pyrano[3,2-b]benzopyran-6-one 5a, which subsequently undergoes a ring contraction–ring expansion mechanism to give the cyclopropanecarbaldehyde 8 followed by its rearrangement to ketene 10via the carbene 9 to furnish ester 4. The various intermediates have been isolated and identified, and their stereochemistry was established from their 1H NMR spectra.

On the mechanism for the phototransformation of 3-alkoxy-2-(2′-furyl)-4-oxo-4H-1-benzopyrans

Photoirradiation of a methanolic solution of 3-alkoxy-2-thienyl-4-oxo-4H-1-benzopyrans with Pyrex filtered UV light leads to cyclised and cyclodehydrogenated angular products involving both thiophene and alkoxy groups. The reaction is initiated through H-abstraction. The product distribution depends upon the substituents on the thiophene ring.

Som N. Dhawan

Papers

Synthesis and anti-inflammatory evaluation of some pyrazolo[3,4- b ]pyridines

Vilsmeier–Haack Reaction on Hydrazones: A Convenient Synthesis of 4-formylpyrazoles:

On the mechanism for the phototransformation of 3-alkoxy-2-(2′-furyl)-4-oxo-4H-1-benzopyrans

Photochemistry of chromones: photoreorganisation of 3-alkoxy-2-thienyl-4-oxo-4H-1-benzopyrans

Photoirradiation of some 3-benzyloxy-2 phenyl-4-oxo-4h-1-benzopyrans