Auxiliary density perturbation theory

A new approach, named auxiliary density perturbation theory, for the calculation of second energy derivatives is presented. It is based on auxiliary density functional theory in which the Coulomb and exchange-correlation potentials are expressed by auxiliary function densities. Different to conventional coupled perturbed Kohn-Sham equations the perturbed density matrix is obtained noniteratively by solving an inhomogeneous equation system with the dimension of the auxiliary function set used to expand the auxiliary function density. A prototype implementation for the analytic calculation of molecular polarizabilities is presented. It is shown that the polarizabilities obtained with the newly developed auxiliary density perturbation approach match quantitative with the ones from standard density functional theory if augmented auxiliary function sets are used. The computational advantages of auxiliary density perturbation theory are discussed, too.     

Indene-based thiazolidinethione chiral auxiliary for propionate and acetate aldol additions

An indene-based thiazolidinethione chiral auxiliary was prepared in two steps from trans-1-amino-2-indanol. Chlorotitanium enolates of this chiral auxiliary delivered excellent diastereoselectivities in propionate and acetate aldol additions. The chiral auxiliary was easily removed to deliver several valuable functionalities.     

Density-functional expansion methods: generalization of the auxiliary basis

The formulation of density-functional expansion methods is extended to treat the second and higher-order terms involving the response density and spin densities with an arbitrary single-center auxiliary basis. The two-center atomic orbital products are represented by the auxiliary functions centered about those two atoms, and the mapping coefficients are determined from a local constrained variational procedure. This two-center variational procedure allows the mapping coefficients to be pretabulated and splined as a function of internuclear separation for efficient look up. The splines of mapping coefficients have a range no longer than that of the overlap integrals, and the auxiliary density appears as a single point-multipole expansion to all nonoverlapping atoms, thus allowing for the trivial implementation of a linear-scaling algorithm. The method is tested using Gaussian multipole expansions, and the effect of angular and radial completeness is explored. Several auxiliary basis sets are parametrized and compared to an auxiliary basis analogous to that used in the self-consistent-charge density-functional tight-binding model, and the method is demonstrated to greatly improve the representation of the density response with respect to a reference expansion model that does not use an auxiliary basis.     

Asymmetric Diels-Alder reactions with a chiral spirodione, (6S, 7S, 10R)-7-Isopropyl-10-methyl-1-oxaspiro[5.5]undec-3-ene-2,5-dione

The synthesis of the title spirodione, a new class of auxiliary based chiral synthon, using (−)-menthone having a unique carbon-carbon bond is described. Diels-Alder reactions were carried out with variety of dienes using the title auxiliary as a chiral dienophile in the presence of diethyl aluminium chloride as Lewis acid catalyst to afford the cycloadduct with good diastereoselectivity. The configurations of the chiral synthon and cycloadducts were determined by X-ray crystallography. Methodology for detachment of the chiral auxiliary from the cycloadducts has been developed.     

On a New Formulation of the Real-Time Propagator

The development of theoretical tools for the study of dynamical phenomena of many-particle systems on the quantum level is a fundamental challenge since many decades. A lot of efforts have been invested on Feynman's path integral approach, however, no computationally tractable method for investigating realistic systems could be developed up to now. In this paper we propose an alternative representation of the real-time many-body evolution operator formulated within the framework of the auxiliary field formalism. Our goal is to derive a new auxiliary field functional integral representation, in which the large oscillations of the functional integrand are reduced, in order to render the auxiliary field approach more attractive for real-time computation. This objective is attained using a generalized version of the method of Gaussian equivalent representation of Efimov and Ganbold [Phys. Stat. Sol. 168 (1991) 165], which eliminates the low-order fluctuations of the auxiliary field from the interaction functional.     

An efficient synthesis of enantiomerically pure unnatural aryl glycinols and aryl glycines

A quick route to enantiomerically pure unnatural aryl glycinols and aryl glycines has been established based on an asymmetric azidation reaction using a chiral benzosultam auxiliary. The synthesis of aryl glycinols involves three steps starting from arylacetic acids, and the chiral auxiliary can be readily recovered.     

Extending synthetic access to proteins with a removable acyl transfer auxiliary

A chemo- and regioselective auxiliary-mediated peptide ligation has been developed that is effective under nonidealized conditions for the synthesis of proteins. This general amide bond ligation utilizes a removable auxiliary that is analogous to the role of cysteine in native chemical ligation, combining chemoselective thioester exchange with efficient regioselective intramolecular acyl transfer. Acid lability and improved ligation efficiency were introduced into the 2-mercaptobenzyl auxiliary by increasing the electron density of the aromatic ring. The 62 amino acid SH3 domain from alpha-spectrin was synthesized using the auxiliary-mediated ligation at a Lys-Gly sequence. The auxiliary was removed with TFA and scavengers from the ligated product. This methodology enables unprotected peptides to be coupled at noncysteine ligation sites expanding the scope of protein synthesis and semisynthesis.     

Asymmetric aldol reactions using chiral CF3-Oxazolidines (Fox) as chiral auxiliary

The aldol reactions of amide enolates derived from a trifluoromethylated oxazolidine (Fox) chiral auxiliary occur in good yields with a moderate anti diastereoselectivity (Li and Na enolates) to a high syn diastereoselectivity (boron enolate). After removal, the Fox chiral auxiliary is very conveniently and efficiently recovered in basic conditions.     

New perspective for natural products synthesis: concise synthesis of (+)-sch 642305 by chiral auxiliary multiuse methodology

The synthesis of (+)-Sch 642305 is an example of chiral auxiliary multiuse methodology, which shows a new perspective for the synthesis of compounds with multiple asymmetric centers. Thus, (+)-Sch 642305 was concisely synthesized from the known compound. Every reaction is stereoselective, and the chiral nonracemic hydrobenzoin worked as chiral auxiliary for desymmetrization of diene, as a template for attaining regio- and stereoselective reactions, as an oxygen source at the C4-position, and as a protecting group of hydroxyl functions. Namely, the chiral auxiliary played a role in every step throughout the synthesis. Furthermore, the synthesis contains a new protocol for obtaining alpha'-alkylated enone compounds.     

Calculation of exchange-correlation potentials with auxiliary function densities

The use of Hermite Gaussian auxiliary function densities from the variational fitting of the Coulomb potential for the calculation of exchange-correlation potentials is discussed. The basic working equations for the energy and gradient calculation are derived. The accuracy of this approximation for optimized structure parameters and bond energies are analyzed. It is shown that the quality of the approximation can be systematically improved by enlarging the auxiliary function set. Average errors of 0.5 kcal/mol are obtained with auxiliary function sets including f and g functions. The timings for a series of alkenes demonstrate a substantial performance improvement.     

A Formal Synthesis of (+)-Cassiol Exploiting Meyers'''' Bicyclic Lactam Methodology

ＩｎｔｒｏｄｕｃｔｉｏｎＩｎ 1988,ｆｒｏｍａｎａｑｕｅｏｕｓｅｘｔｒａｃｔｉｏｎｏｆＣｈｉｎｅｓｅｃｉｎ ｎａｍｏｎ ,ｗｈｉｃｈｈａｓｌｏｎｇｂｅｅｎｕｓｅｄｉｎｔｈｅｔｒａｄｉｔｉｏｎａｌＣｈｉ ｎｅｓｅｍｅｄｉｃｉｎｅａｓａｄｉａｐｈｏｒｅｔｉｃ ,ａｎｔｉｐｙｒｅｔｉｃ ,ｏｒａｎａｌｇｅｓｉｃａｇｅｎｔ,Ｆｕｋａｙａａｎｄｃｏ ｗｏｒｋｅｒｓｉｓｏｌａｔｅｄｃａｓｓｉｏｓｉｄｅ (1)ａｎｄｆｏｕｎｄｔｈａｔｔｈｉｓｃｏｍｐｏｕｎｄｐｏｓｓｅｓｓｅｄｒｅｍａｒｋａｂｌｅａｎｔｉｕｌ ｃｅｒｏｇｅｎｉ…     

Synthesis of novel chiral spirodione, (6R,7R)-7-phenyl-1-oxaspiro[5.5]undec-3-ene-2,5-dione: application to the asymmetric Diels-Alder reaction with high π-facial selectivity

The synthesis of the title spirodione, a new class of auxiliary based chiral synthon using (−)-trans-2-phenylcyclohexanol and its application to the asymmetric Diels-Alder reaction are described. Methodology for detachment of the chiral auxiliary from the cycloadduct has been developed.     

A novel design of a levoglucosenone derived chiral auxiliary

A two-step general approach to a new chiral auxiliary starting from levoglucosenone is reported. The compound is obtained by a [4+2] cycloaddition reaction with anthracene followed by a diastereoselective reduction of the C-2 keto function in high overall yield. The auxiliary has been used as chiral template in an asymmetric Diels-Alder reaction of the corresponding acrylic ester derivative with cyclopentadiene and shown to be efficient for asymmetric induction.     

Second generation levoglucosenone-derived chiral auxiliaries. Scope and application in asymmetric Diels-Alder reactions

Chiral alcohols were designed and easily prepared from levoglucosenone, a biomass-derived valuable synthon. These alcohols were tested as chiral auxiliaries in asymmetric Diels-Alder reactions between the corresponding acrylates with acyclic and cyclic dienes. The regio, stereo, and facial selectivity varied from very good to excellent, depending upon the benzylic substitution of the auxiliary and the diene employed. As a consequence, after removal of the auxiliary, the resulting carboxylic acid derivatives were obtained in 72-99% ee.     

A photoremovable ligation auxiliary for use in polypeptide synthesis

A photoremovable auxiliary for use in peptide synthesis via the native chemical ligation method is described. A 2-mercapto-1-(2-nitrophenyl)ethylamine (Mnpe-amine) moiety was attached to the N-terminus of a peptide via the periodate oxidation of a seryl peptide. The resulting peptide was then ligated to a peptide thioester, and UV (365 nm) irradiation resulted in the removal of the auxiliary from the peptide.     

Achieving high selectivity and facile displacement with a new thiol auxiliary for boron-mediated aldol reactions

Synthesis of a new thiol auxiliary (1) is readily achieved (in five or six steps, >74% overall yield from norephedrine) and is shown to give high diastereoselectivity in boron-mediated anti-aldol reactions with a range of aldehydes. This new thiol auxiliary may be directly displaced by a range of nucleophiles under very mild conditions, to give the corresponding phosphonate esters, alcohols, acids, SNAC thiolesters, and methyl esters.     

Cleavage of a chiral auxiliary using RCM on an especially sterically crowded alkene: Syntheses of chiral carbo- and heterocycles

Chiral 1,5-, 1,6-, and 1,7-dienes generated in 3–4 steps from chiral auxiliary p-menthane-3-carboxaldehyde undergo RCM with notable discrepancies in reactivity depending on the nature and number of substituents flanking the central double bond. The chiral auxiliary is thus cleaved releasing a carbo- or heterocycle in the process. Special features concerning the RCM on these especially crowded systems are discussed.     

Asymmetric synthesis of sulfinamides using (-)-quinine as chiral auxiliary

A process has been designed and demonstrated for the asymmetric synthesis of sulfinamides using quinine as auxiliary. A variety of chiral sulfinamides including N-alkyl sulfinamides with diverse structure were prepared in good yields and excellent enantioselectivity starting from easily available and inexpensive reagents. The auxiliary quinine could be recovered and recycled.     

A PEGylated Photocleavable Auxiliary Mediates the Sequential Enzymatic Glycosylation and Native Chemical Ligation of Peptides

Research aimed at understanding the specific role of glycosylation patterns in protein function would greatly benefit from additional approaches allowing direct access to homogeneous glycoproteins. Herein the development and application of an efficient approach for the synthesis of complex homogenously glycosylated peptides based on a multifunctional photocleavable auxiliary is described. The presence of a PEG polymer within the auxiliary enables sequential enzymatic glycosylation and straightforward isolation in excellent yields. The auxiliary‐modified peptides can be directly used in native chemical ligations with peptide thioesters easily obtained by direct hydrazinolysis of the respective glycosylated peptidyl resins and subsequent oxidation. The ligated glycopeptides can be smoothly deprotected by UV irradiation. We apply this approach to the preparation of variants of the epithelial tumor marker MUC1 carrying one or more Tn, T, or sialyl‐T antigens.     

Application of acyclic chiral auxiliaries on alkylation reactions

The application in alkylation reactions of an acyclic chiral auxiliary is described. The synthesis is straightforward from a chiral primary amine and a double acylation. A characteristic of this auxiliary is its modular design formed by an achiral part (acyl) and a chiral component (primary amine) so it can be tuned for different reactions without difficulty. The alkylation proceeds with excellent diastereoselectivity because the conformational flexibility of the enolate is restricted by the formation of a chelate and the allylic 1,3-strain.