Lactones correlation table

Evaluation of the HH ROESY (c) verifies the amino acid sequence of the cyclopentapeptide lactone ring attached to C-9 of actinocin by means of the NOE induced spatial correlation signals la-belled a d in the formula C. The a- and (3-protons of threonine in both cyclopentapeptide lactone rings are sufficiently separated but close to each other. This applies to the other amino acid protons with the exception of TV-methylvaline, in which proton signals overlap (Table 55.1). Therefore, starting from the a- and [3-protons of threonine 8H = 4.61 and 5.75), the sequence Thr-Vai-Pro-Sar-MeVal attached to C-l of actinocin is similarly verified in the HH ROESY as shown in formula C. The connection Sar-MeVal is established by the spatial correlations d between the 72-protons of sarcosine and the A7-methyl-protons of 7V-methylvaline in both rings (SH = 4.71/2.92 and 4.78/2.89). 

Recently, several papers have reported the isolation of new lactarane lactones, possessing the methyl group at C-3 either cis or trans to H-2, and the lactone carbonyl group either at C-5 (5-lactaranolides. Tables 11-13) or at C-13 (13-lactaranolides, Tables 16-17). Differentiation between these structural alternatives on the basis of spectroscopic data alone has been often risky, especially when only a single isomer is at hand. Therefore, chemical correlations, synthesis of the possible isomers, and molecular mechanics calculations have always been performed in order to corroborate spectroscopic informations. 

Furantriol (18.27), isolated from L. mitissimus (84), is one of the few lactarane sesquiterpenes in which one of the gem-methyl groups at C-11 is oxidized and it was chemically correlated (82) with lactarorufin B (11.71), another example of this kind. The Polish authors suggested that lactone 11.71 was enzymatically formed from furan 18.27, and that a C-15 oxidized sesquiterpene of the velutinal type was the common precursor of both compounds in the mushroom (84). Actually, the possibility for the C-15 methyl group to be oxidized at an early stage of the lactarane biosynthesis seems to be confirmed by the recent finding of C-15 hydroxylated protoilludane sesquiterpenoids (5.1 and 5.2) in L. violascens (23) (Table 5). 

Tables 3 and 4 contain results from a study of a series of coumarins and fiirocoumarins in, 1,2-dibromoethane, which found that the lactone carbonyl signal consistently appeared near 350 ppm more variability was seen for the single bonded oxygen, especially for the furocoumarins, typically appearing at 220 ppm [85]. Synthetic 3-aryl coumarins also exhibit 6(C=0) and 5(-0-) values near those mentioned above [86]. Recently, a study of a series of 7-substituted-4-methylcoumarins, with a wide range in electronic character of the substituents, demonstrated that the carbonyl signal is quite sensitive to substituent effects and that the NMR chemical shift is reasonably well correlated with the carbonyl oxygen AMI estimated electron density [87].

Analysis of the CH correlation signals (CH COSY/CH COLOC) for the protons at 7.38 and 5.54ppm (Table 40.1) shows this ring to be a five-membered lactone. The CH correlation signals with the protons at 4.65ppm (AB system of methylene protons on C-10) and 2.04ppm (methyl group) identify and locate an acetate residue (CO ... 

Many of the observed attributes of enzymes arise by natural selection in order to help the host organism survive and reproduce. Benner et al. have proposed that one such attribute, the stereospecificities of dehydrogenases, has functional significance based on stereochemical arguments (18, 79). The central features of their functional model can be summarized as follows. The stereospecificities of dehydrogenases acting on alcohols are correlated with the equilibrium constant for the alcohol-carbonyl redox reaction as listed in Table IV (18). Enzymes catalyzing reactions where the eq is <10 " ilf transfer the pro-S proton from NADH when is >10"" Af, the pro-R proton is transferred. Thus the more readily reduced carbonyl compounds use the pro-R proton, but the more difficult to reduce carbonyl compounds use the pro-S proton. The proposed correlation is restricted to simple aldehydes and ketones (i.e., without additional chemistry that would influence the equilibrium constant, such as cyclizations of polyols or formation of lactones). The natural substrate of the enzyme must be well... 

Most biological activities of STLs have been related to the presence of electrophilic structure elements, which undergo covalent reaction with functional biological macromolecules resulting in their deactivation [1-3]. In this respect, a,P-unsaturated carbonyl groups as well as epoxide and free aldehyde groups have to be considered reactive partial structures. The alkylation of free cysteine residues in enzymes and other functional proteins by STLs has in many instances been held responsible for STL bioactivity and there is a clear correlation between the presence of such residues in proteins and their susceptibility to inactivation by STLs [1-3], see section Alkylant Sesquiterpene Lactones . It was therefore of interest to investigate the distribution of such potential reactive sites (PRS) in the structures of the 4861 STLs (Table 1). 

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