RESUMO
We repeat the earliest claimed [2]catenane synthesis, reported by Wasserman over 60 years ago, in order to ascertain whether or not a nontemplate, statistical synthesis by acyloin macrocyclization does indeed form mechanically interlocked rings. The lack of direct experimental evidence for Wasserman's catenane has led to it being described as a "prophetic compound", a technical term used in patents for claimed molecules that have not yet been synthesized. Contemporary synthetic methods were used to reconstruct Wasserman's deuterium-labeled macrocycle and other building blocks on the 10-100 g reaction scale necessary to generate, in principle, â¼1 mg of catenane. Modern spectrometric and spectroscopic tools and chemical techniques (including tandem mass spectrometry, deuterium nuclear magnetic resonance (NMR) spectroscopy, and fluorescent tag labeling) were brought to bear in an effort to detect, isolate, and prove the structure of a putative [2]catenane consisting of a 34-membered cyclic hydrocarbon mechanically linked with a 34-membered cyclic α-hydroxyketone.
RESUMO
We report on the preparation of a decapeptide through the parallel operation of two rotaxane-based molecular machines. The synthesis proceeds in four stages: (1) simultaneous operation of two molecular peptide synthesizers in the same reaction vessel; (2) selective residue activation of short-oligomer intermediates; (3) ligation; (4) product release. Key features of the machine design include the following: (a) selective transformation of a thioproline building block to a cysteine (once it has been incorporated into a hexapeptide intermediate by one molecular machine); (b) a macrocycle-peptide hydrazine linkage (as part of the second machine) to differentiate the intermediates and enable their directional ligation; and (c) incorporation of a Glu residue in the assembly module of one machine to enable release of the final product while simultaneously removing part of the assembly machinery from the product. The two molecular machines participate in the synthesis of a product that is beyond the capability of individual small-molecule machines, in a manner reminiscent of the ligation and post-translational modification of proteins in biology.
RESUMO
Hyperjaponesâ A-E and hyperjaponolsâ A-C are complex natural products of mixed aromatic polyketide and terpene biosynthetic origin that have recently been isolated from Hypericum japonicum. We have synthesized hyperjaponesâ A-E using a biomimetic, oxidative hetero-Diels-Alder reaction to couple together dearomatized acylphloroglucinol and cyclic terpene natural products. Hyperjaponeâ A is proposed to be the biosynthetic precursor of hyperjaponolâ C through a sequence of: 1)â epoxidation; 2)â acid-catalyzed epoxide ring-opening; and 3)â a concerted, asynchronous alkene cyclization and 1,2-alkyl shift of a tertiary carbocation. Chemical mimicry of this proposed biosynthetic sequence allowed a concise total synthesis of hyperjaponolâ C to be completed in which six carbon-carbon bonds, six stereocenters, and three rings were constructed in just four steps.
Assuntos
Materiais Biomiméticos/síntese química , Hypericum/química , Policetídeos/síntese química , Terpenos/síntese química , Materiais Biomiméticos/química , Conformação Molecular , Policetídeos/química , Estereoisomerismo , Terpenos/químicaRESUMO
Protected cyclohexanol and cyclohex-2-enol substrates, containing benzyl ether and benzoate ester moieties, were designed to fit into the active site of the Tyr96Ala mutant of cytochrome P450cam. The protected cyclohexanol substrates were efficiently and selectively hydroxylated by the mutant enzyme at the trans C-H bond of C-4 on the cyclohexyl ring. The selectivity of oxidation of the benzoate ester protected cyclohexanol could be altered by making alternative amino acid substitutions in the P450cam active site. The addition of the double bond in the cyclohexyl ring of the benzoate ester protected cyclohex-2-enol has a debilitative effect on the activity of the Tyr96Ala mutant with this substrate. However, the Phe87Ala/Tyr96Phe double mutant, which introduces space at a different location in the active site than the Tyr96Ala mutant, was able to efficiently hydroxylate the C-H bonds of 1-cyclohex-2-enyl benzoate at the allylic C-4 position. Mutations at Phe87 improved the selectivity of the oxidation of 1-phenyl-1-cyclohexylethylene to trans-4-phenyl-ethenylcyclohexanol (92%) when compared to single mutants at Tyr96 of P450cam.
Assuntos
Álcoois/química , Álcoois/metabolismo , Carbono/química , Sistema Enzimático do Citocromo P-450/metabolismo , Álcoois/síntese química , Benzoatos/química , Domínio Catalítico , Cicloexanos/química , Cicloexenos/química , Sistema Enzimático do Citocromo P-450/química , Ligação de Hidrogênio , Modelos Moleculares , OxirreduçãoRESUMO
The total synthesis of peniphenones A-D has been achieved via Michael reactions between appropriate nucleophiles and a common o-quinone methide intermediate. This strategy, which was based on a biosynthetic hypothesis, minimized the use of protecting groups and thus facilitated concise syntheses of the natural products. The most complex target, the benzannulated spiroketal peniphenone A, was synthesized enantioselectively in nine linear steps from commercially available starting materials.
Assuntos
Antibacterianos/isolamento & purificação , Benzoquinonas/síntese química , Produtos Biológicos/síntese química , Indolquinonas/química , Penicillium/química , Antibacterianos/química , Antibacterianos/farmacologia , Benzoquinonas/química , Benzoquinonas/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Rhizophoraceae/microbiologia , EstereoisomerismoRESUMO
The total synthesis of ent-penilactone A and penilactone B has been achieved via biomimetic Michael reactions between tetronic acids and o-quinone methides. A five-component cascade reaction between a tetronic acid, formaldehyde, and a resorcinol derivative that generates four carbon-carbon bonds, one carbon-oxygen bond, and two stereocenters in a one-pot synthesis of penilactone A is also reported.
Assuntos
Furanos/química , Indolquinonas/química , Policetídeos/química , Policetídeos/síntese química , Biomimética , Catálise , Estrutura Molecular , EstereoisomerismoRESUMO
A structure revision for the recently isolated fungal meroterpenoids, cytosporolides A-C, is suggested based on biosynthetic speculation and reinterpretation of existing spectroscopic data. The structure revision is supported by a biomimetic synthetic study, featuring a [4 + 2] cycloaddition reaction between a presumed o-quinone methide intermediate and ß-caryophyllene.