Spontaneous chiral resolution of a coordination polymer with distorted helical structure consisting of achiral building blocks

Reaction of achiral 2,5-diphenyl-3,4-di(3-pyridyl)cyclopenta-2,4-dien-1-one (2) with ZnCl2 and HgBr2, respectively, afforded the helically chiral coordination polymers [(2)ZnCl2]infinity and [(2)HgBr2]infinity, which show spontaneous chiral resolution, forming colonies of homochiral crystals.     

New chiral building blocks from tetrabromocyclopropene and furan

The cyclocondensation of tetrabromocyclopropene and furan leads directly to a halogenated oxabicyclo[3.2.1]octadiene derivative. Over the past several years, we have utilized these compounds as intermediates for natural product synthesis. Herein, we describe the preparation of nonracemic dibromoenone building blocks from the racemic cycloadduct. Conversion of the adduct to a mixture of tartrate-derived ketals followed by separation of the diastereomers and hydrolysis allows for the formation of novel chiral synthons with either absolute configuration.     

Convenient synthesis and isolation of trifluoromethylthio-substituted building blocks

Various aryl-, heteroaryl-, and alkyl mercaptanes (RSH, 1a–r) were treated with a slight excess of NaH suspended in DMF to make the appropriate sodium thiolates (RSNa), which then reacted with 1.3 equivalent of CF₃I at room temperature for overnight to afford the appropriate trifluoromethyl sulfides (CF₃SR, 2) in fair to good yields. The radical chain alkylation reaction was effective without the use of UV irradiation with all but three substrates (thiosalicylic acid, 1k; 2-mercaptobenzimidazole, 1q; and 3-mercaptopropionic acid, 1r).Steam-distillation was found as an effective and easy to upscale means for the isolation of these volatile and water immiscible sulfides. The CF₃I reagent gas was conveniently weighed and delivered to the reaction mixture by the balloon technique or as a preliminary made stock solution in DMF or DMSO. The sulfides 2 obtained here were assayed by GC and characterized by ¹H, ¹³C, ¹⁹F NMR and MS spectroscopy.     

Synthesis of chiral building blocks for cephalostatin analogues

The present paper describes the synthesis of 5‐azido‐6‐ketones (14) and 6‐hydroxy‐5‐ketone (20) from Hajos Wiechert ketone as chiral building blocks for cephalostatin analogues. The synthesis of symmetric cephalostatin analogue from 6‐hydroxy‐5‐ketone has also been reported. The characterization of the each synthesized compounds was carried out by IR, ¹H‐NMR, ¹³C‐NMR and High resolution Mass Spectrometry.     

Hydrotalcite catalysis for the synthesis of new chiral building blocks

The use of hydrotalcites for the synthesis of two chiral building blocks in a simple way is described as a new and green methodology. The synthesis of these compounds implies a regioselective Baeyer–Villiger reaction in a very selective way with ulterior opening and lactonisation. This methodology should be considered green for the use of hydrogen peroxide as the only oxidant and hydrotalcites as the catalyst, and because no residues are produced apart from water. The procedure is very adequate for using in gram scale, in order to increase the value of the obtained compounds. The conditions are excellent and can be applied for nonstable compounds, as they are very mild. The synthesised compounds are magnific starting materials for the synthesis of biologically active or natural compounds. The use of a cheap, commercial and chiral compound as carvone disposable in both enantiomeric forms adds an extra value to this methodology.     

Preparation of new chiral building blocks via asymmetric catalysis

Highly enantio- and stereoselective preparation of some new chiral building blocks with baker's yeast or the CBS catalyst is described.     

Asymmetric synthesis of alkaloids using polyfunctionalized chiral building blocks

Enantiopure N‐sulfinyl‐δ‐amino‐β‐ketoesters and isoquinolones, prepared from sulfinimines (N‐sulfinyl imines) are a new class of polyfunctionalized chiral building blocks. These building blocks provide easy access to enantiomerically pure, functionalized piperidines and tetrahydroisoquinolines with a minimum of chemical manipulation and protecting‐group chemistry. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:486–492, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10090     

Rules on chiral and achiral molecular transformations

The properties of chiral and achiral transformations between mirror images ofn-dimensional point sets are investigated. Several rules are proven, relevant to chirality-preserving and chirality-abandoning molecular transformations.     

A chiral pool approach to the synthesis of optically active tetrahalo norbornyl building blocks

Optical antipodes of the mono- and disubstituted polyhalo norbornyl derivatives were prepared in excellent yields. The monosubstituted derivatives 7 were obtained with good enantiopurities. A kaleidoscopic change in the product formation and distribution was observed by changing the chronology of reactions.     

Improved synthesis of the enantiomers of propafenone using chiral building blocks

Summary A short and efficient synthesis of the enantiomers of the antiarrhythmic drug propafenone (1) is described using both (R)-isopropylideneglycerol tosylate and (S)-glycidyl tosylate as chiral building blocks. The key step of the high yield synthesis is the acetalization of the carbonyl group in 1-(2-hydroxyphenyl)-3-phenyl-1-propanone (2) which allows application of mild reaction conditions in the subsequent alkylation of the phenolic hydroxy group.With our best wishes dedicated to Prof. Dr.H. Achenbach on the occasion of his 65^th birthday     

Synthesis of chiral building blocks for use in drug discovery

In the past decade there has been a significant growth in the sales of pharmaceutical drugs worldwide, but more importantly there has been a dramatic growth in the sales of single enantiomer drugs. The pharmaceutical industry has a rising demand for chiral intermediates and research reagents because of the continuing imperative to improve drug efficacy. This in turn impacts on researchers involved in preclinical discovery work. Besides traditional chiral pool and resolution of racemates as sources of chiral building blocks, many new synthetic methods including a great variety of catalytic reactions have been developed which facilitate the production of complex chiral drug candidates for clinical trials. The most ambitious technique is to synthesise homochiral compounds from non-chiral starting materials using chiral metal catalysts and related chemistry. Examples of the synthesis of chiral building blocks from achiral materials utilizing asymmetric hydrogenation and asymmetric epoxidation are presented.     

New chiral building blocks from acetovanillone using lipase A and B from Candida antarctica

Acetovanillone has been used as the starting material for the synthesis of a series of secondary alcohols, which were resolved by lipase catalyzed esterification. 1-(4-Benzyloxy-3-methoxyphenyl)ethanol was efficiently resolved using immobilized lipase B from Candida antarctica (Novozym 435, CAL-B), whereas immobilized lipase A from C. antarctica (Novozym 735, CAL-A) was the lipase of choice for the resolution of the corresponding 2-bromo- and 2-chloro-derivatives. The enantioenriched alcohols are new building blocks for potential use in the synthesis of bioactive compounds.     

Enzyme assisted syntheses of chiral building blocks for isosters of diglycerides,phospholipids and PAF

Lipase catalyzed desymmetrizations of suitably substituted, achiral 1,3-diols lead to the corresponding chiral building blocks of high enantiomeric purities, starting materials for the synthesis of isosteric carba-analogues of 1,2-sn-diglycerides and phospholipids with interesting biological activities. Lipase catalyzed resolutions of the corresponding ether derivatives lead to the corresponding building blocks for carba-analogues of PAF.     

Asymmetric induction during photocyclization of chiral and achiral alpha-oxoamides within achiral zeolites

The photochemistry of 31 alpha-oxoamides capable of undergoing gamma-hydrogen transfer has been examined within zeolites. These molecules, upon excitation, yield two products--a beta-lactam and oxazolidinone--in solution, both resulting from gamma-hydrogen transfer. While in benzene the major product is oxazolidinone, within an MY zeolite, the main product is a beta-lactam. In this investigation, we have focused our attention on asymmetric induction in the formation of the beta-lactam product. Two approaches--using a chiral inductor and chiral auxiliary--have been employed. While in solution, in the presence of chiral inductors, achiral alpha-oxoamides yield beta-lactams with zero enantioselectivity; within zeolites, an ee of up to 44% has been achieved. Alpha-oxoamides appended with a chiral auxiliary gave beta-lactams with less than 5% diastereoselectivity in solution while within zeolites, the same alpha-oxoamides gave the products with de's of up to 83%. Such a remarkable influence of zeolites is attributed to an alkali ion interaction with the reactant alpha-oxoamides and to the confined environment of the zeolite interior. At this stage, we have not been able to provide a model with predictive power and further work is needed to understand this valuable asymmetric induction strategy.     

Synthesis of novel enantiopure fluorinated building blocks from acyclic chiral allylsilanes

[reaction: see text] Homochiral beta-fluorinated gamma,delta-unsaturated carboxylic acids with an allylic fluorinated stereogenic center are available from the corresponding enantiopure allylsilanes. The key step for introduction of the fluorine substituent is an electrophilic fluorodesilylation reaction carried out in the presence of Selectfluor. Reduction of the resulting beta-fluorinated pentenoic acid into the corresponding fluorinated alcohol was also performed leading to the formation of an enantiopure second-generation fluorinated building block.     

Enzymatic syntheses of chiral building blocks with trifluoromethyl or pentafluoroethyl groups

A number of optically active allylic alcohols with a trifluoromethyl or a pentafluoroethyl group were prepared by the biological reduction of the corresponding ketones with active fermenting baker's yeast.     

Calixarene amino acids; building blocks for calixarene peptides and peptide-dendrimers

A modular strategy towards receptor macromolecules is presented, which combines synthetically diverse peptide synthesis with highly functional calixarene chemistry. The design and synthesis of calix[4]arene amino acids 1a-f, calix-lysines, is described, which were used as construction blocks to assemble nanoscale, multivalent entities—calix-peptides 2 and calix-peptide-dendrimers 3.     

Microporous 3-D chiral metal-organic framework with a quartzlike topology based on an achiral building unit

A zinc coordination polymer, Zn(IN)₂ · 2H₂O (1) (HIN = isonicotinic acid), has been synthesized and characterized by IR, elemental analysis, thermogravimetric analysis, and single crystal X-ray diffraction. This compound crystallizes in the chiral space group P6₂ with a = 15.512(3), b = 15.512(3), c = 6.262(2) Å, V = 1304.9(5) ų, and Z = 3. The O and N atoms of the IN ligand are coordinated to a Zn^II ion, locking the asymmetry of the IN ligand and transferring this asymmetry throughout the crystal structure to “direct” the formation of a chiral network. The structure of 1 is characteristic of a 3-D quartz-like framework, which contains hetero-chiral helical channels (pseudo-trigonal and hexagon channels) alternately along the c-axis. Compound 1 exhibits high stability and intense fluorescent emission at room temperature.