RESUMO
Briarellins, a subset of C2-C11 cyclized cembranoids, were proposed to contain a C3-C14 ether or lactone bridge, similar to asbestinins. However, the total synthesis of the proposed structure of briarellin J revealed a misassignment. We revisited briarellins, computationally, with the help of a recently developed hybrid DFT/parametric method, DU8+, and revised the structures of briarellin C14-C3 ε-lactones to new structural types containing either a C14-C11 or C14-C12 lactone bridge. The original structures of briarellin and asbestinin ethers were confirmed.
Assuntos
LactonasRESUMO
Covering: up to 2018With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data is intended to enhance the transparency of experimental protocols, augment the reproducibility of reported outcomes, including biological studies, become a regular component of responsible research, and thereby enrich the integrity of NP research and related fields.
Assuntos
Produtos Biológicos/química , Espectroscopia de Ressonância Magnética/métodos , Conformação Molecular , Reprodutibilidade dos TestesRESUMO
Correction for 'The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research' by James B. McAlpine et al., Nat. Prod. Rep., 2018, DOI: .
RESUMO
A highly convergent, enantioselective total synthesis of brevetoxin A is reported. The development of a [X+2+X] Horner-Wadsworth-Emmons/cyclodehydration/reductive etherification convergent coupling strategy allowed a unified approach to the synthesis of two advanced tetracyclic fragments from four cyclic ether subunits. The Horner-Wittig coupling of the two tetracyclic fragments provided substrates that were explored for reductive etherification, the success of which delivered a late-stage tetraol intermediate. The tetraol was converted to the natural product through an expeditious selective oxidative process followed by methylenation.
Assuntos
Éteres Cíclicos/síntese química , Toxinas Marinhas/síntese química , Oxocinas/síntese química , Catálise , Ciclização , Éteres Cíclicos/química , Toxinas Marinhas/química , Estrutura Molecular , Oxocinas/química , EstereoisomerismoRESUMO
Brevetoxin A is a decacyclic ladder toxin that possesses 5-, 6-, 7-, 8-, and 9-membered oxacycles, as well as 22 tetrahedral stereocenters. Herein, we describe a unified approach to the B, E, G, and J rings based upon a ring-closing metathesis strategy from the corresponding dienes. The enolate technologies developed in our laboratory allowed access to the precursor acyclic dienes for the B, E, and G medium-ring ethers. The strategies developed for the syntheses of these four monocycles ultimately provided multigram quantities of each of the rings, supporting our efforts toward the completion of a convergent synthesis of brevetoxin A.
Assuntos
Éteres/síntese química , Toxinas Marinhas/síntese química , Oxocinas/síntese química , Alquilação , Ciclização , Éteres/química , Toxinas Marinhas/química , Estrutura Molecular , Oxocinas/química , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
[reaction: see text] Highly diastereoselective acetate aldol additions using chlorotitanium enolates of mesityl-substituted N-acetyloxazolidinethione and N-acetylthiazolidinethione auxiliaries are reported. These additions proceed in high yields and diastereoselectivities (93:7 to 98:2) for aliphatic, aromatic, and ,-unsaturated aldehydes. Double diastereoselective acetate aldol additions are also reported and are found to proceed in high yields and diastereoselectivities (90:10 to 97:3).
Assuntos
Acetatos/química , Aldeídos/química , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Oxazolidinonas/química , Estereoisomerismo , Tiazolidinas/químicaRESUMO
The synthesis of the briarane-brianthein A core has been accomplished utilizing an extension of the dianionic Ireland-Claisen rearrangement to establish the C1 quaternary carbon and the adjacent C10 ring juncture stereocenters. Two sequential ring-closing metathesis reactions were exploited to construct the 6-10 trans fused ring system.
Assuntos
Diterpenos/química , Carbono , Estrutura Molecular , EstereoisomerismoRESUMO
The conversion of a substituted dioxinone to a pyrone was used in an improved synthesis of the AB spiroketal subunit of the spongistatins. This transformation occurred via a hetero-Diels-Alder reaction of an acyl ketene with butyl vinyl ether. A double diastereoselective Mukaiyama aldol reaction is used to provide the hetero-Diels-Alder precursor.
Assuntos
Macrolídeos/síntese química , Pironas/química , Animais , Antineoplásicos , Catálise , Macrolídeos/química , Estrutura Molecular , Poríferos/química , EstereoisomerismoRESUMO
Construction of the unique bicyclic bis-ether core of the macrolide (+)-sorangicin A has been achieved. This fragment was prepared by utilizing a one-pot cascade of three bond forming events. An epoxide opening of the epoxy tosylate 2 led to the formation of the tetrahydropyran and subsequently to a second epoxide. Finally, a second epoxide opening closed the tetrahydrofuran ring. The bicyclic fragment was synthesized in just nine steps from (E)-cinnamaldehyde.
Assuntos
Aminoglicosídeos/síntese química , Éteres/química , Aminoglicosídeos/química , EstereoisomerismoRESUMO
[reaction: see text] The enantioselective synthesis of the carbon skeleton of 6-deoxyerythronolide B has been achieved in 23 linear steps from propionaldehyde. The synthesis relies on an iterative approach employing an asymmetric acyl-thiazolidinethione propionate aldol reaction to establish eight of nine stereogenic centers. The remaining stereogenic center at C6 was set through a Myers alkylation employing a complex alkyl iodide.
Assuntos
Eritromicina/análogos & derivados , Tiazolidinas/química , Aldeídos/química , Eritromicina/síntese química , Eritromicina/química , Estrutura MolecularRESUMO
[structure: see text] A stereoselective synthesis of SCH 351448 has been completed. Twelve of the fourteen stereogenic centers were established through chiral enolate reactions, and six key C-C bonds were formed by metathesis reactions.
Assuntos
Lactonas/síntese química , Lactonas/química , Micromonospora/química , Estrutura Molecular , EstereoisomerismoRESUMO
A second-generation synthesis of the BCDE fragment of brevetoxin A is described. Novel reactions were developed that extend the utility of the asymmetric glycolate alkylation reaction and improve scale-up to provide gram quantities of the B and E subunits. Significant improvements to the convergent assembly of the tetracycle were also realized. In addition, formation of the A ring lactone was accomplished to complete the ABCDE pentacycle.
Assuntos
Toxinas Marinhas/síntese química , Oxocinas/síntese química , Estrutura MolecularRESUMO
[reaction: see text] An enantioselective total synthesis of (-)-mucocin has been completed. A combination of asymmetric glycolate aldol additions and ring closing metathesis reactions were exploited to construct the C18-C34 and C7-C17 fragments. A selective cross-metathesis reaction was employed as the key step to couple two complex fragments.
Assuntos
Lactonas/síntese química , Piranos/síntese química , Lactonas/química , Estrutura Molecular , Piranos/química , Rollinia/química , EstereoisomerismoRESUMO
[reaction: see text] A stereoselective synthesis of the GHIJ fragment of brevetoxin A utilizing a convergent assembly strategy is described. Glycolate alkylation, ring-closing metathesis, and Hosomi-Sakurai reactions were central operations in the construction of the G ring and J ring subunits, which were united through a Horner-Wadsworth-Emmons coupling. Subsequent dehydrative cyclization produced an endocyclic enol ether that was further elaborated to the tetracyclic GHIJ fragment of brevetoxin A.
Assuntos
Toxinas Marinhas/síntese química , Oxocinas/síntese química , Toxinas Marinhas/química , Estrutura Molecular , Oxocinas/química , EstereoisomerismoRESUMO
[structure: see text] The de novo synthesis of the C9 and C27 sugar subunits (2) and (3), respectively, of the potent antitumor agent, apoptolidin, has been accomplished. A titanium tetrachloride-mediated asymmetric anti glycolate aldol addition was utilized to establish the 4' and 5' stereogenic centers of each of the three monosaccharides. Elaboration of the aldol adducts efficiently provided the three sugar units. A beta-selective glycosidation completed the construction of the C27 disaccharide.
Assuntos
Carboidratos/química , Macrolídeos/química , Carboidratos/síntese química , Carbono/química , Estrutura Molecular , EstereoisomerismoRESUMO
A stereoselective synthesis of the BCDE fragment of brevetoxin A has been completed. anti-Glycolate aldol, glycolate alkylation, and ring-closing metathesis reactions were employed as key bond-forming events. A convergent assembly strategy was employed that relied on a Horner-Wadsworth-Emmons union of two complex fragments. Subsequent cyclization and dehydration led to efficient generation of an intermediate endocyclic enol ether, which was advanced to a tetracyclic fragment. [reaction: see text]
Assuntos
Éteres Cíclicos/síntese química , Toxinas Marinhas/síntese química , Oxocinas/síntese química , Hidrocarbonetos Policíclicos Aromáticos/síntese química , Alquilação , Catálise , Ciclização , Éteres Cíclicos/química , Toxinas Marinhas/química , Estrutura Molecular , Oxocinas/química , Hidrocarbonetos Policíclicos Aromáticos/química , EstereoisomerismoAssuntos
Produtos Biológicos/síntese química , Diterpenos/síntese química , Éteres Cíclicos/síntese química , Animais , Antozoários/química , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Ciclização , Diterpenos/química , Diterpenos/isolamento & purificação , Éteres Cíclicos/química , Éteres Cíclicos/isolamento & purificação , Estrutura MolecularRESUMO
In the past few years, the microtubule stabilizing agent (-)-laulimalide has attracted considerable attention, as it could constitute a potential treatment for cancer. Several total syntheses of (-)-laulimalide have now been reported. This review summarizes available biological data and synthetic approaches to (-)-laulimalide, reported prior to July 2002.
Assuntos
Excipientes/síntese química , Microtúbulos , Paclitaxel/análogos & derivados , Paclitaxel/síntese química , Taxoides , Animais , Excipientes/metabolismo , Humanos , Macrolídeos , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Paclitaxel/metabolismoRESUMO
[reaction: see text] The enantioselective synthesis of the (+)-leucascandrolide A macrolactone has been achieved in 20 linear steps from 1,3-propanediol. The key steps in the synthesis are a reductive cleavage of bicyclic ketal 5 to establish the C15 stereogenic center and a diastereoselective aldol of the boron enolate of methyl ketone 3 to aldehyde 4 in preparation for a heteroconjugate addition for the introduction of the C3 stereocenter.
Assuntos
Sesquiterpenos/síntese química , Aldeídos/síntese química , Aldeídos/química , Cetonas/química , Estrutura Molecular , Sesquiterpenos/química , EstereoisomerismoRESUMO
[reaction: see text] A highly diastereoselective anti aldol addition utilizing a variety of N-glycolyloxazolidinethiones has been developed. Enolization of an N-glycolyloxazolidinethione with titanium (IV) chloride and (-)-sparteine followed by addition of an aldehyde activated with additional TiCl(4) resulted in highly anti-selective aldol additions, typically with no observable syn isomers. Allyl-protected glycolates demonstrated the highest levels of selection and yields, although O-benzyl and O-methyl glycolyloxazolidinethiones also performed well.