EPC synthesis of (+)-heptelidic acid

Summary An EPC (enantiomerically pure compound) synthesis of the antibiotic natural product (+)-heptelidic acid (1) is presented. Key step of the synthesis is a conjugate addition of the acetal protected vinyl cuprate4 to the auxiliary shielded enoate5n which gives the adduct7n as a single diastereomer. After cleavage of the acetal protecting group and of the chiral auxiliary the enantiomerically pure -ketoester12 has been obtained which has been transformed to the title compound1 (11 steps starting from5n, 10.6% overall yield).

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EPC-Synthese von (+)-heptelidsäure

Zusammenfassung Eine EPC-Synthese (EPC = enantiomerically pure compound) des antibiotischen Naturstoffes (+)-Heptelidsäure (1) wird präsentiert. Schlüsselschritt der Synthese ist dieMichael-Addition des acetal-geschützten Vinylcuprates4 an das auxiliargeschützte Enoat5n, wobei das Addukt7n in diastereomerenreiner Form erhalten wird. Nach der Abspaltung der Acetalschutzgruppe und des chiralen Auxiliars läßt sich der enantiomerenreine -Ketoester12 herstellen, der in die Titelverbindung1 umgewandelt werden kann (11 Stufen ausgehend von5n, 10.6% Gesamtausbeute).

     

Diastereoselective conjugate addition of 1-(α,β-unsaturated acyl)hydantoin with nucleophiles

A diastereomeric conjugate addition of dialkylaluminum chloride to 1-(α,β-unsaturated acyl)hydantoin provided the corresponding alkyl adduct with inducted chirality in the β-position. Treatment of 1-(α,β-unsaturated acyl)hydantoin with Gilman reagent in the presence of Lewis acid also gave the same product. In this reaction, diethylaluminum chloride was the most effective Lewis acid and the absolute configuration of the major adduct at the β-position of acyl group depended on the kinds of existing metals.     

An efficient conjugate hydrothiocyanation of chalcones with a task-specific ionic liquid

A new and efficient method of conjugate hydrothiocyanation of chalcones along with the preparation of a probe for demonstrating the utility of the resulting β-thiocyanato ketones in heterocyclic synthesis is reported. Chalcones undergo an efficient conjugate hydrothiocyanation with the task-specific ionic liquid (TSIL), 1-n-butyl-3-methylimidazolium thiocyanate ([bmim]SCN) followed by reaction with AcONH₄ or an amine to afford chemically and pharmaceutically interesting 2-amino-1,3-thiazines at room temperature in a one-pot procedure. After isolation of the product, the ionic liquid [bmim]OH could be used for the synthesis of [bmim]SCN, thus allowing recycling of the TSIL for further use.     

A simple procedure for the synthesis of γ-hydroxy-α,β-(E)-alkenoic esters: formal synthesis of (+)-macrosphelides A and B

A highly trans-selective conjugate reduction of γ-hydroxy-α,β-alkynoic esters to produce γ-hydroxy-α,β-(E)-alkenoic esters using LiAlH₄ is reported. The application of this methodology is demonstrated by a formal synthesis of the potent cell-cell adhesion inhibitors (+)-macrosphelides A and B.     

桥链冠醚卟啉胆固醇酯的表观质子化常数

用光度法测得三种桥链冠醚卟啉和二种卟啉胆固醇酯的质子化常数，并用ＨＭＯ法进行了量子化学计算，讨论了取代基的电子效应及空间效应对常数的影响。     

Conjugate addition of aromatic amines to ethenetricarboxylates

The conjugate addition of amines is considered to be a useful reaction in synthetic organic chemistry. The reaction of reactive electrophilic olefins, ethenetricarboxylates, and aromatic amines with and without catalytic Lewis acids such as ZnCl₂ and ZnBr₂ at room temperature gave amine adducts in high yields. The products were converted to α-amino acid, dl-aspartic acid derivatives. Using Lewis acids such as Sc(OTf)₃ and Zn(OTf)₂ at higher temperature (40-80 °C), the reaction of ethenetricarboxylates and N-methylaniline gave an aromatic substitution product. A catalytic enantioselective conjugate addition using a chiral Lewis acid was also investigated. For example, the reaction of 1,1-diethyl 2-tert-butyl ethenetricarboxylate with N-methylaniline in the presence of chiral bisoxazoline-Cu(II) complex in THF at −20 °C for 17 h gave an amine adduct in 91% yield and 78% ee. On the other hand, the reaction with aniline and primary aniline derivatives gave adducts with almost no ee%.     

A new synthesis of amides and γ-lactones based on the conjugate addition of lithium enolate of amides to 1-chlorovinyl p-tolyl sulfoxides

Reaction of 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from chloromethyl p-tolyl sulfoxide and ketones or aldehydes, with lithium enolate of N,N-dimethylacetamide gave the adducts in good to quantitative yields. The adducts were converted to several kinds of amides in high overall yields. Treatment of the adducts with trifluoroacetic anhydride in the presence of NaI resulted in the formation of γ-tolylsulfanylated γ-lactones in high yields. The scope and limitations of this method and the mechanism of the reactions are also discussed. These procedures offer a new and effective method for the synthesis of amides and γ-lactones having substituents on the β-carbon from N,N-dimethylacetamide with carbon elongation.     

Global convergence result for conjugate gradient methods

Conjugate gradient optimization algorithms depend on the search directions,

Periodically preconditioned conjugate gradient-restoration algorithm

In this paper, the problem of minimizing a nonlinear functionf(x) subject to a nonlinear constraint (x)=0 is considered, wheref is a scalar,x is ann-vector, and is aq-vector, withq<n. A conjugate gradient-restoration algorithm similar to those developed by Mieleet al. (Refs. 1 and 2) is employed. This particular algorithm consists of a sequence of conjugate gradient-restoration cycles. The conjugate gradient portion of each cycle is based upon a conjugate gradient algorithm that is derived for the special case of a quadratic function subject to linear constraints. This portion of the cycle involves a single step and is designed to decrease the value of the function while satisfying the constraints to first order. The restoration portion of each cycle involves one or more iterations and is designed to restore the norm of the constraint function to within a predetermined tolerance about zero.The conjugate gradient-restoration sequence is reinitialized with a simple gradient step everyn–q or less cycles. At the beginning of each simple gradient step, a positive-definite preconditioning matrix is used to accelerate the convergence of the algorithm. The preconditioner chosen,H ₊, is the positive-definite reflection of the Hessian matrixH. The matrixH ₊ is defined herein to be a matrix whose eigenvectors are identical to those of the Hessian and whose eigenvalues are the moduli of the latter's eigenvalues. A singular-value decomposition is used to efficiently construct this matrix. The selection of the matrixH ₊ as the preconditioner is motivated by the fact that gradient algorithms exhibit excellent convergence characteristics on quadratic problems whose Hessians have small condition numbers. To this end, the transforming operatorH ₊ ^1/2 produces a transformed Hessian with a condition number of one.A higher-order example, which has resulted from a new eigenstructure assignment formulation (Ref. 3), is used to illustrate the rapidity of convergence of the algorithm, along with two simpler examples.     

在Armijo型线搜索下共轭梯度法簇的全局收敛性

本文我们讨论了一簇共轭梯度法，它可被看作是FR法和DY法的凸组合．我们提出了两种Armijo型线搜索，并在这两种线搜索下，讨论了共轭梯度法簇的全局收敛性．