Conformational control in the cyclization of hydrogen-bonded supramolecular polymers

Bifunctional 2-ureido-4[1H]-pyrimidinone (UPy) derivatives can form small cyclic oligomers as well as long supramolecular polymers in chloroform solutions using the quadruple hydrogen-bonding motif. Ring-chain equilibria of a set of supramolecular monomers containing methyl-substituted alkyl linkers between the hydrogen-bonding UPy moieties were investigated by (1)H NMR spectroscopy and viscometry. The data were characterized in terms of critical concentration (CC, denoting the onset of polymerization) and equilibrium cyclic dimer concentration (EDC, representing preorganization of the monomer toward selective formation of cyclic dimer). Methyl substituents in the monomer were found to promote conformations favorable for cyclic dimerization, leading to an increase in both the EDC and the CC with respect to unsubstituted monomer. Furthermore, we observed an odd-even effect in the CC and EDC with increasing length of the linker between the hydrogen-bonding units. The combined results allow tuning of the critical concentration over a broad range and offer detailed information on the correlation between monomer structure, conformation, and polymerizability which may provide new insights for the study and design of other ring-chain equilibria or helix-random coil transitions.     

Synthesis of Z- and E-polyunsaturated isoprenoids with functional groups initiating electrophilic cyclization

Summary Separate olefination has been carried out for the carbonyl groups of 1,8-diketo-4-methyl-4Z-nonene and 1,12-diketo-4,8-dimethyl-4E, 8E-tridecadiene into 1,5-polyenes which were prepared for electrophilic cyclization.Deceased.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 821–823, April, 1981.     

Stereochemistry of protonation and mercuration of trisubstituted double bond during cyclization of isoprenoids

Conclusions Initiation of the reaction for the cyclization of isoprenoids by acids proceeds as a nonstereospecific process at the 2,3 bond, while when this reaction is initiated by mercury salts it proceeds as a stereospecific reaction.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1151–1153, May, 1973.     

Biosynthesis of isoprenoids in Escherichia coli: stereochemistry of the reaction catalyzed by farnesyl diphosphate synthase

[formula: see text] Farnesyl diphosphate (FPP) synthase from Escherichia coli catalyzes the condensation of isopentenyl diphosphate (IPP) and geranyl diphosphate (GPP) with selective removal of the pro-R hydrogen at C2 of IPP, the same stereochemistry observed for the pig liver, yeast, and avian enzymes.     

Conformational analysis and stereochemistry of the reduction of 2-alkoxymethyl-4-oxopiperidines

The isomer with an axially oriented alkoxymethyl group predominates in the equilibrium mixture of 1-aklyl-2,5-dimethyl-2-alkoxymethyl-4-piperidones investigated under both alkaline and acidic equilibrium conditions, and its percentage increases as the volume of the alkoxy group increases in the order Me, Et, iso-Pr. The reduction of 4-ketopiperidines that contain a polar function in the 2 position follows the same principles as those that obtain when it is absent, i.e., exclusively the equatorial alcohols are obtained in the case of reduction with lithium and ethanol in liquid ammonia, whereas primarily the axial alcohols are obtained in the case of reduction with sodium borohydride. The selectivity of the reduction increases on passing from the free bases to the hydrochlorides.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 503–506, April, 1979.     

Conformational analysis and absolute stereochemistry of ‘spongian’-related metabolites

New degraded and rearranged diterpenoids, 5-8, have been isolated from the Antarctic sponge Dendrilla membranosa. The structure and relative stereochemistry of these compounds were determined by spectroscopic data. The absolute stereochemistry of 5 was determined by spectroscopic data using a chiral reagent. Conformational studies allowed us to assign also the absolute stereochemistry of 6-8, as well as those previously isolated spongian-derived metabolites with known relative stereochemistries.     

Conformational control on remote stereochemistry in the intramolecular Pauson–Khand reactions of enynes tethered to homoallyl and homopropargyl alcohols

An intramolecular Pauson–Khand reaction of enynes derived from homoallyl and homopropargyl alcohols is described. 2-Furyl substituted homoallyl and homopropargyl alcohols are easily and efficiently resolved through enzymatic resolution in a high ee (93–99%) with a known stereochemistry. Each enantiomerically enriched enyne affords the conformationally most stable diastereomeric cyclopenta[c]pyran ring system.     

The synthesis of 1-cyclohexyl-2-phenyl-3-nitroaziridine and the stereochemistry of cyclization

The title compound was synthesized by the cyclization of α,β-dibromonitrostyrene with three moles of cyclohexylamine. Evidence for the steric course of the cyclization reaction is also reported.     

Synthesis of purine- and pyrimidine-substituted heptadienes. The stereochemistry of cyclization and cyclopolymerization products

A series of 1,6-heptadienes, substituted in the 4 position with nucleic acid bases 1-6, have been synthesized via Mitsunobu condensations. Guanine, adenine, thymine, and uracil derivatives can be prepared directly by coupling the protected base with 1,6-heptadien-4-ol (7). However, coupling protected cytosine and 7 gives an O-alkylated product. Thus, the cytosine derivative must be prepared from the uracil-substituted heptadienes via the triazole. The free-radical addition of CCl(4) and BrCCl(3) to these adducts was investigated. In all cases, both 1:1 and 1:2 adducts were obtained. The 1:1 adduct was identified as the cyclized product of the initially formed 5-hexen-1-yl radical. The cyclization takes place in a stereospecific manner, with only one of the four possible diastereomers resulting. NMR studies indicate that all substituents are cis in this product. In the case of the addition of CCl(4) to the uracil-substituted heptadiene, this conclusion was confirmed by an X-ray structure determination of the isolated cyclized product. The free-radical-initiated cyclocopolymerizations of 1-6 with SO(2) gave 1:1 copolymers with cis-linked five-membered rings. Two-dimensional NMR studies on poly(2-SO(2)) showed predominately the cis-syn isomer while poly(6-SO(2)) has an approximately equal amount of cis-syn and cis-anti isomers.     

Terpestacin core structure. control of stereochemistry

[reaction: see text] The alpha-hydroxycyclopentenone core structure of terpestacin has been prepared in a model system through an allene ether Nazarov cyclization of an alkylidene-gamma-butyrolactone followed by regio- and stereoselective alkylation reactions. The stereochemistry at C15 (terpestacin numbering) has been used to control stereochemistry at C1 and at C23. The use of E-alkylidene-gamma-butyrolactones extends the scope of the cationic cyclopentannelation reaction.     

Mechanism and stereochemistry of enzymatic cyclization of 24,30-Bisnor-2,3-oxidosqualene by recombinant beta-amyrin synthase

Recombinant beta-amyrin synthase from Pisum sativum converted 24,30-bisnor-2,3-oxidosqualene into a 3:1:0.2 mixture of 29,30-bisnor-beta-amyrin, 29,30-bisnorgermanicol, and 29,30-bisnor-delta-amyrin. Further, enzyme reactions with [23-13C]- and [23,23-2H]-labeled isotopomers demonstrated that the cyclization did not proceed through formation of a lupanyl primary cation with a five-membered E-ring, but an electrophilic addition of the tetracyclic C-18 cation on to the terminal double bond directly generated a thermodynamically favored pentacyclic secondary cation with a less-strained six-membered E-ring. Interestingly, the formation of the three regioisomers suggested that the absence of the terminal methyl groups resulted in a structural perturbation in the folding conformation of the E-ring of the oleanyl cation at the active site of the enzyme.     

Deuterium-labeling studies establishing stereochemistry at the oxypalladation step in Wacker-type oxidative cyclization of an o-allylphenol

The stereochemical pathway (syn or anti) of the oxypalladation step was studied in the palladium(II)-catalyzed Wacker-type cyclization of stereospecifically deuterated 6-(2-hydroxyphenyl)-3-deuteriocyclohexenes, cis-3-d-1 and trans-3-d-1, giving dihydrobenzofuran derivatives. The stereochemistry was determined to be syn in the reaction catalyzed by a dicationic palladium(II) catalyst generated from Pd(MeCN)4(BF4)2 and (S,S)-ip-boxax in the presence of benzoquinone in methanol, while it is mainly anti in the reaction catalyzed by PdCl2(MeCN)2 in the presence of a chloride ion.     

Conformational control of hydrogen-bonded aromatic bis-ureas

The phenylurea moiety is a ubiquitous synthon in supramolecular chemistry because it contains strong complementary hydrogen bonding groups and is synthetically very accessible. Here we investigate the possibility to strengthen self-association by conformational preorganization of the phenylurea moiety. In fact, we show that it is possible to strongly enhance intermolecular interactions between hydrogen bonded aromatic bis-ureas by substitution at the ortho positions of the phenylurea groups. Ortho substituents enforce a noncoplanar conformation of the urea and phenyl moieties better suited for hydrogen bonding. Substitution by methyl groups is more efficient than with larger groups, probably because of reduced steric hindrance. These effects have been demonstrated in the case of two different supramolecular architectures, which points to the probable generality of the phenomenon. In addition, this study has led to the discovery of a new bis-urea able to form very stable self-assembled nanotubes in toluene up to high temperatures (boiling point) or low concentrations (10(-7) M) and in chloroform down to 3 × 10(-4) M.     

Regiochemical control in intramolecular cyclization of methylene-interrupted epoxydiols

[reaction: see text] Methylene-interrupted epoxydiols have multiple regiochemical routes for cyclization. The 5-exo process is the most prevalent under acidic conditions. However, the regioselectivity can be controlled by the appropriate choice of acid promoter and pendant groups adjacent to the epoxide. The 5-exo product is obtained exclusively without the presence of a carbocation-stabilizing pendant group. Alkenyl and thiophenyl groups adjacent to the epoxide alter the regioselectivity and enable access to the 5-endo tetrahydrofuran and 6-endo tetrahydropyran products.