Colman

Colman, 1994] Colman, P. Strncture-based drug design. Curr. Opinion Struct. Biol. 4 (1994) 868-874... 

GABRIEL COLMAN Rearrangement Synthesis of isoquinolines by rearrangement ol phthahmides. 

C Chothia, AM Lesk, A Tramontano, M Levitt, SJ Smith-Gill, G Air, S Sheriff, LA Padlan, D Davies, WR Tulip, PM Colman, S Spmelh, PM Alzari, RJ Poljak. Conformation of immunoglobulin hypervariable regions. Nature 342 877-883, 1989. 

Figure 5.9 The six four-stranded motifs in a single subunit of neuraminidase form the six blades of a propeller-like structure. A schematic diagram of the subunit structure shows the propeller viewed from its side (a). An idealized propeller structure viewed from the side to highlight the position of the active site is shown in (b). The loop regions that connect the motifs (red in b) in combination with the loops that connect strands 2 and 3 within the motifs (green in b) form a wide funnel-shaped active site pocket, [(a) Adapted from P. Colman et ah, Nature 326 358-363, 1987.]...

Colman, P.M., Varghese, J.N., Laver, W.G. Structure of the catalytic and antigenic sites in influenza virus neuraminidase. Nature 303 41-44, 1983. 

Colman, P.M. Structure of antibody-antigen complexes implications for immune recognition. Adv. Immunol. 43 99-132, 1988. 

Colman, P.M., et al. Three-dimensional structure of a complex of antibody with influenza virus neuraminidase. Nature 326 358-363, 1987. 

The Gabriel-Colman rearrangement entails reaction of the enolate of a maleimidyl acetate (2) to provide isoquinoline 1,4-diol 3. ... 

In 1900, Gabriel and Colman reported the preparation of phthalimidoyl acetate 4 They had anticipated saponifying 4 with sodium ethoxide and were surprised to find, rather than hydrolysis, rearrangement to 5. The identity of the product was confirmed by hydrolysis of the newly formed ester and concomitant decarboxylation to provide 6, which was hydrogenated to the known isocarbostyril (7). 

The Gabriel-Colman reaction has been used to prepare 3-alkyl isoquinoline 1,4-diols. Phthalimides 8 and 9 rearrange as expected when treated with alkoxides. Further treatment with sodium ethoxide results in decarboxylation and the expected isoquinolinone 1,4-diols 12 and 13. 

The Gabriel-Colman reaction can be used to prepare isoquinoline-1,4-diols regioselectively by the use of unsymmetrically substituted phthalimides. Reaction of phthalimide 32 with sodium ethoxide in ethanol provides a 1 7 mixture of 33 34. It was rationalized that attack at carbon b is preferred because of its greater steric accessibility and diminished electron density compared to carbon a. In spite of the reasonable regioselectivity observed m this reaction, the Gabriel-Colman reaction has not been substantially investigated in the preparation of non-symmetrically substituted isoquinolines. 

Shortly after Gabriel and Colman reported cinchomeronylacetic ester, Pels reported a similar quinolinimidoacetic ester (40) to provide a 1,6-naphthyridine (41).The structure of the isolated compound was not unambiguously determined for more than 30 years.More recently, the reaction has been shown to produce both 41 and 42 in a 3 1 ratio... 

The most widely used variant of the Gabriel-Colman is the conversion of saccharine derivatives to benzothiazine derivatives. The reaction has been extensively studied as benzothiazines are important pharmacophores, particularly in the oxicam class of antiinflammatories. The first reported instance of this transformation was in 1956 where 43 was treated with sodium methoxide to provide 44. The rearrangement also works with esters " and some amides " in addition to ketones. 

The mechanism of this variant of the Gabriel-Colman reaction has been investigated. Treatment of saccharine derivatives 45-48 with 1-2 equivalents of sodium alkoxide at room temperature provides esters 49-52 in good yields treatment of 45-48 with sodium alkoxide at reflux provides the expected benzothiazines 53-56. Increased concentration leads to higher yields. 

The methiodide of quinazoline (63) was studied by Gabriel and Colman and shown to possess structure 64. Gabriel s evidence has been checked by later workers and the substitution in the... 

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