Spiro biological activity

Figure Bl.2.11. Biologically active centre in myoglobin or one of the subunits of haemoglobin. The bound CO molecule as well as the proximal and distal histidines are shown m addition to the protohaeme unit. From Rousseau D L and Friedman J M 1988 Biological Applications of Raman Spectroscopy vol 3, ed T G Spiro (New York Wiley). Reprinted by pennission of John Wiley and Sons Inc.

Spiro-(indoline-isoxazolidines) 137, exhibiting interesting biological activities, were prepared in modest yields, by the cycloaddition reaction between ethyl (3-indolylidene)-acetate 135 and various substituted a,N-diphenylnitrones 136 under solvent-free conditions (Scheme 48). The reaction conducted under conventional heating in an oil bath did not proceed even after 20 h, especially when it was carried out without solvent [87]. 

Moreover, this catalyst is also effective in the oxidation of a spiro-cycUc acetal of 5-methoxy-l,2,3,4-tetrahydronaphthalenone to palmarumycin CP2 [35], a biosynthetic precursor to the preussomerin class of natural products exhibiting a wide range of biological activity. 

The cyclic ammonium ylide/[l,2]-shift approach has been successfully applied by West and Naidu to a key step in the total synthesis of (—)-epilupinine, one of the biologically active lupin alkaloids. Cu(acac)2-catalyzed diazo decomposition of enantiomeric pure diazoketone 160 in refluxing toluene generates a spiro ammonium ylide 161 and 162, which then undergoes [l,2]-shift to give rise to a quinolizidine skeleton as a mixture of diastereomers (95 5) (Scheme Major diastereomer 164 has enantiomeric purity of 75% ee. The partial retention of stereo-... 

Keywords Biological activity Cholesterol absorption inhibitors Ketene-imine cycloaddition Spiroazetidin-2-ones Spiro-(3-lactams Synthetic intermediates (3-Lactamase inhibitors... 

Hussain and Nizamuddin have synthesized 1, 3-dithiolane substituted spiro-(5-lactams (Scheme 27) since 1, 3-dithiolane derivatives exhibit various biological activities like fungicidal, bactericidal, and insecticidal [97]. The starting thiadia-zoles 104 were treated with sodium hydroxide and carbon disulfide to get the corresponding disodium dithiocarbamate 105, which were stirred with 1,2-dichlo-roethane to obtain 106. Cyclocondensation of 106 with chloroacetyl chloride in dry dioxane in the presence of triethylamine gave the spiro-(5-lactams 107. These spiro-(5-lactams were found to exhibit antifungal activity 75-85% at 100-ppm concentration against P. oryzae and F. oxysporum. 

Excellent yields are also obtained in spiro-adducts formed by the condensation of azomethine ylid thus generated, with 3-arylidene-flavanone derivatives at room temperature in the presence of trifluomethylacetic acid in toluene. These molecules are both flavonoids and spiro compounds, two classes of naturally occurring substances which exhibit biological activities 419... 

Spirolactone moieties are important components of some biologically active steroids that possess antitumor activity. A prelude to formation of the spiro unit is the introduction of an allyl side chain into a steroidal ketone. This reaction can be accomplished in good yield by the Barbier reaction of allyl bromide, ketone, and iodine-activated magnesium in ether. With 5a-cholestan-3-one, 51 and 48% of the epimeric allyl alcohols are isolated. With 3(i-(tetrahydropyran-2-yloxy)-5a-androstan-17-one, 98% of the allyl alcohol is isolated [39]. 

The synthesis of spiro y-lactones has been extended to the synthesis of spiro -lactones. This one-pot transformation of 1,3-dienes reacted with epoxides, mediated by Rieke magnesium to spiro -lactones in good isolated yields, was recently reported [15]. Much work has been done to elucidate novel synthetic routes for these types of molecules [16]. In particular, -substituted 5-lactones have recently attracted considerable attention, mainly because molecules of this class include many natural products that exhibit substantial biological activity [17]. However, most methods for the synthesis of these molecules require... 

Marine sponges of the genus Dysidea are a rich source of structurally unique and biologically active compounds, including spiro-sesquiterpenes such as spirodysin and dehydroherbadysinolide, furanosesquiterpenes based on the furodysinin and furodysin skeletons, brominated diphenyl ethers, polychlorinated alkaloids and other compounds [99-103],... 

The biological activity of the diterpenoids of the aphidicolin-stemodin series makes these compounds attractive targets. The total synthesis of stemodin (96) has been described.172 The key spiro-centre at C-9 was constructed by the internal aldol condensation of the keto-aldehyde (97) to afford (98). Several stereoselective syntheses of aphidicolin have been reported with different solutions to the problem... 

Chromone derivatives, in particular 2-spiro-chroman-4(lF/)-ones, are ubiquitous in nature and possess various biological activities which include antiarrhythmic, anti-HIV, antidiabetic, acetyl-CoA carboxylase (ACC) inhibitor, vanilloid receptor antagonist, growth hormone secretagogues, histamine receptor antagonist, and... 

In terms of the yield and reaction rate, the Reformatskii reaction is a rather convenient route to biologically active 3-methylene-substituted 2-oxo-l,2-oxaphosphacyclanes 85, including those having a spiro-structure (Scheme 52) [116, 117]. Metal-catalysed formation of the P-C bond was also successfully used for the synthesis of similar phostones [118]. Thus, 3-methylene-1,2-oxaphosphacycla-nes 85 were formed in reasonable yields by palladium-catalysed intramolecular cyclization in a series of hydrophosphoryl compounds 86 (Scheme 52). 

Hussain and Nizamuddin [97] combined the 1,3-dithiolane moieties with azetidin-2-ones for the study of different biological activities. The spiro-p-lactams I (Fig. 10) have been screened against A. niger, P. oryzae, F. oxysporum, and... 

Fig. 13. Biological active center in hemoglobin and myoglobin. The filled black circles represent the heme skeletal atoms, and the black circles with white dots represent the peripheral groups of the heme. The cross-hatched circles represent the atoms of the proximal and distal histidine and the white circles with black dots a bound CO ligand. [From D. L. Rousseau and J. M. Friedman, in Biological Applications of Raman Spectroscopy (T. G. Spiro, ed,), Vol. 3, p. 133. Wiley, New York, 1988.]...

C22H25NO8, Mr 431.44, colorless cryst., mp. 162-163.5 °C, (a)[) -5° (CHjOH), isolated from cultures of Pseudeurotium ovalis and Aspergillus fumi-gatus. P. A contains a substituted l-oxa-7-aza-spiro[4.4]nonane skeleton. No biological activities have been reported. Several natural derivatives are known, they differ from P. A in the aliphatic side chain or do not possess an 0-methyl group. 

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