Cyclic analogue

Alicyclic Hydrocarbons. These refer to cyclic analogues of aliphatic hydrocarbons and are named accordingly, using the piefix cyclo-." Their properties are similar to their open-chain aliphatic counterparts. Alicyclic hydrocarbons are subdivided into monocyclic (cycloalkanes, cycloalkenes, cycloalkynes, cycloalkadienes, etc.) and polycyclic aliphatic compounds. Monocyclic aliphatic structures having more than 30 carbon atoms in the ring are known, but those containing 5 or 6 carbon atoms are more commonly found in nature [47, p. 28]. 

A. lCBr titration of Enniatin B in methanol. Since exchange of cation between solution and carrier is relatively rapid only one signal is seen per chemically distinct carbonyl. The titration shows the magnitude of the chemical shift observed. Since Enniatin B may be considered a cyclic analogue of Gramicidin A, these chemical shifts indicate the magnitudes of chemical shifts that can be expected in the Gramicidin A channel (see Fig. 6 and 13) for direct interaction of carbonyl with cation. 

The cyclic disilazane 2012, which is readily accessible by treatment of 45 with NH3, reacts with the urea-H202 adduct to give, in 68% yield, the liquid cyclic analogue 2013 of BTSP 1249 2013 seems, to be more hindered and thus less reactive than BTSP 1949 [183] (Scheme 12.53). 

Each enantiomer of 67 was earlier obtained by an a-chymotrypsin-catalysed resolution of its diethyl ester 68 or its cyclic analogue 69, followed by chemical hydrolysis (Scheme 6)7°... 

Figure 1 Structural formulas of cyclic analogues of phenylalanine and tyrosine.

Recently, a structure-inhibition-activity relationship study revealed that carbapenem derivatives could lead to a new class of specific inhibitors of bacterial /3-lactamases [54], Indeed, phosphonyl derivatives, 5.16, and their cyclic analogues, 5.17 - i.e., structures not based on the /1-lactam nucleus -can also afford effective inhibitors of /3-lactamases [55][56],... 

Trispyrazolylborates are models for tris-histidine active sites in zinc enzymes, e.g., the matrix metalloproteinases involved in breakdown of extracellular matrices. Inhibition of these metalloproteinases may prove valuable in the treatment of, inter alios, cancer and arthritis, so efforts are being made to find appropriate ligands to block the zinc active site. The search has recently moved on from hydroxamates to hydroxypyridinones - l-hydroxy-2-pyridinone is a cyclic analogue of hydroxamic acid. As reported in Section II.B.2 earlier, hydroxypyridinones form stable five-coordinate complexes on reaction with hydrotris(3,5-phenylmethylpyrazolyl)borate zinc hydroxide. Modeling studies suggest that hydroxypyridinonate ligands should be able to access the active site in the enzyme with ease (110). 

Earlier investigations have indicated that the network of disulfide linkages found within /3-defensins is not required for antimicrobial activity. An investigation by Kliiver et al. has demonstrated that disulfide connectivity in a particular context is not required for antimicrobial activity. Indeed, HBD-3 derivatives lacking disulfide bonds were found to be as active as their cyclic analogues. This is in agreement with a previous study by Hoover et in which a linear variant of full-length HBD-3 retained antimicrobial activity... 

Open-chain enehydrazines [156] are very unstable substances, but their cyclic analogues, 3-pyrazolines [157], have been the subject of... 

Cyclic analogues of hydrazones [151], 2-pyrazolines, show both protonation and alkylation on N-1, as has already been discussed on page 326. The sp nitrogen (which distinguishes these systems from enamines) does not appear to play any direct part. 

Suggested preferred conformations can be fixed by cyclization. Cystine has been used to obtain cyclic analogues of Org 2766 viz. H-Cys-Glu-His-Cys-D-Lys-Phe-OH, H-Cys-Ala-Ala-Cys-D-Lys--Phe-OH and H-Cys-Ala-Ala-Phe-D-Lys-Cys-OH (patent application 0052028 of Roussel-UcIaf), and the peptides were tested for activity in the pole-jumping test. Unfortunately, one cannot conclude from their data if cyclization has resulted in an increase or decrease in activity since no reference peptide has been included to compare potencies. In the literature cyclization of [Lys ]ACTH--(5-10) (the COOH group of Gly with the 6-NH2 function of Lys ) has been reported the resulting peptide was inactive in steroidogenesis (61). Increase of the ring size with three atoms (a Gly residue), however, resulted in a peptide that was more active... 

B pMeBHA (HF) cyclic analogues of hGH (6-13) BOP, BOP/ HOBt, HBTU/HOBt, DIC/HOBt HPLC/MS BOP, BOP/HOBt, HBTU/HOBt (3 equiv) in DMF, 7h [366]... 

The one-step synthesis of further tri- and tetracyclic pteridine derivatives from 2-aminopyrazine 153 has also been described <2001JHC1173>. Cyclic analogues of A -[bis(methylthio)methylene]amino reagents such as 2-(methylthio)-2-thiazoline, 5,6-dihydro-2-(methylthio)-4//-l,3-thiazine, 2-(methylthio)-2-imidazoline, 2-(methylthio)-l,4,5,6-tetrahydro-pyrimidine, 2-(methylthio)-2-pyrazine, and 2-chloropyrimidine reacted with aminopyrazine 153 to afford thiazolo/thia-zino[2,3-3]- 159 ( = 1 (53%), n = 2 (42%)), imidazo/pyrimidino[2,l-/ ]- 160 ( = 1 (53%), = 2 (57%)), pyrazino[2,l-/ ]-161 (21%), and pyrimido[2,l-/ ]-pteridine 162 (42%) derivatives, respectively. 

Similar cyclic analogues of substituted phenylalanines 74,75 and histidine 28 have been prepared and incorporated into biologically active peptides. 

Dorofeenko and his coworkers have extended this route to the synthesis of a range of cyclic analogues of pyrylium salts. Thus, cyclohexenylacetophenone affords the reduced isobenzopyrylium salt (635) on treatment with acetic anhydride (67MI22402) and 2-(indol-2-yl)cyclohexanone yields the indolo[2,3-rf]pyrylium salt (636) in the same way (69ZOB716). The yields in these reactions are much improved, a feature which may be attributable to the conformational preference for the structure shown for the enone rather than a conjugated arrangement of double bonds. 

Here a single number is used to indicate the number of carbon atoms in the original nomomer, i.e., nylon-11 ( eleven" not one-one ), in some instances the cyclic analogue or lactam is more accessible than the amino acid and is polymerized by a ring-opening rather than condensation mechanism ... 

This section covers the coordination chemistry of aza macrocycles taken as rings of nine or more members, with three or more ring nitrogen atoms, and not included in Chapter 21.1. These ligands have many properties in common with their non-cyclic analogues (Chapter 13) and also have properties in common with other cyclic polydentate ligands (Chapters 21.1 and 21.3). The subject was comprehensively reviewed in 1979,1-6 and in general references included therein will not be listed. 

The properties of the aza macrocycle compounds generally resemble those of their non-cyclic analogues, and only a few more specifically macrocyclic aspects are described. 

For the cyclic triamines, Ni11 compounds hydrolyze slowly (e.g. for [12]aneN3 k IO-6 s-1)42 but the Cun compounds react at about the same rate as non-cyclic analogues.43... 

For Ni11 and Cu" complexes of [15]aneN5 the reaction is second order in [H+],44 while for [Cu([l 8]aneN6]2+ the reaction is third order in [H+], indicating that the step from tetra- to tri-dentate is rate-determining in both cases. The rates for these larger macrocycles are comparable with those of non-cyclic analogues. 

No reactions of t with protic solvents have been reported however, its cyclic analogue 1,2-diphenylcyclobutene (7) reacts with the protic solvents methanol, acetic acid, and water, to yield adducts 85 and 86 (eq. 28). The proposed mechanism for the formation of 85 and 86 involves the formation of singlet exciplex followed by proton transfer to yield a cyclobutyl cation 87. Stereoselective nucleophilic capture of 87 by solvent from its less hindered side yields 85, while skeletal rearrangement of 87 yields the cyclopropylmethyl cation 88, which reacts with solvent to yield 86 ... 

Thiols, like alcohols, react readily with carbonyl compounds. The resulting hemithioacetals (102), thioacetals (103) and their cyclic analogues (104) and (105) are of considerable synthetic importance. These compounds are more stable to acid hydrolysis than their oxygen analogues but can be hydrolyzed under mild conditions in the presence of metal ions such as Ag(I) (equation 29). The synthetic importance of the metal ion-promoted hydrolyses has led to the publication... 

Masuno MN, Pessah EM, Olmstead MM, Molinski TF (2006) Simplified Cyclic Analogues of Bastadin-5. Structure-Activity Relationships for Modulation of the RyRl/FKBP12 Ca+2 Channel Complex. J Med Chem 49 4497... 

Systematic investigations into this reaction have been undertaken and showed that for straight-chain aralkyl hydroperoxides and their cyclic analogues the (R)-alcohol forms, whereas the stereoselection is the opposite for branched hydroperoxides. The reaction could be applied to functionalized hydroperoxides such as a- and (3-hydroperoxy esters or hydroperoxy alcohols with good to excellent diastereo- and enantioselectivities. Up to 99% ees were obtained for small, sterically non-hindered substrates, whereas for tertiary hydroperoxides and for substrates with substituents at the co-position neither good ees nor useful turnover numbers have been reported. HRP reacts very sluggishly also with sterically demanding silyl-substituted allyl hydroperoxides. 

In yet another successful application of the traditional Noyori three-component reaction, Ftirstner and co-workers took advantage of their remarkable alkyne metathesis reaction [21] to synthesize therapeutically promising cyclic analogues of prostaglandins [22] such as PGE2-l-15-lactone 34 (Figure 12.1) [23]. 

Acyclic carbohydrate derivatives containing unsaturation, with some exceptions, exhibit much of the chemistry already described for cyclic analogues, and their usefulness should not be overlooked. Unsaturated derivatives of alditols can be made, for example, by standard eliminations from alditol v/r-disulfonates or epoxides or by /f-eliminations from O-substituted 1-deoxy-l-nitroalditols and 1-deoxy-l-sulfonylalditols. Additions of hydrogen and ammonia to the unsaturated nitroalditols made in this way offer, respectively, routes to 2-deoxy- and 2-amino-2-deoxyaldoses.255... 

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