ABSTRACT
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.
Subject(s)
LactonesABSTRACT
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.
Subject(s)
Biological Products/chemistry , Magnetic Resonance Spectroscopy/methods , Molecular Conformation , Reproducibility of ResultsABSTRACT
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: .
ABSTRACT
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.
Subject(s)
Diterpenes/chemistry , Carbon , Molecular Structure , StereoisomerismABSTRACT
A dianionic Ireland-Claisen rearrangement of chiral, nonracemic α-methyl-ß-hydroxy allylic esters has been developed that proceeds with high diastereoselectivity and provides products containing three contiguous stereogenic carbons, including a quaternary center. The potential utility of the rearrangement for complex molecule synthesis is also demonstrated.
Subject(s)
Anions/chemistry , Carbon/chemistry , Propionates/chemical synthesis , Catalysis , Esters , Molecular Structure , Propionates/chemistry , StereoisomerismABSTRACT
Synthesis of the C1-C6 and C7-C23 fragments of the proposed structure of iriomoteolide 1a has been accomplished. Key steps include a cross metathesis to form the C15-C16 E olefin and a chelation controlled Grignard addition to form the tertiary alcohol at C14. Notably, 7 of the 9 stereocenters of the proposed structure have been set using various aldol reactions employing metallo enolates of thiazolidinethiones.
Subject(s)
Macrolides/chemical synthesis , Thiazolidines/chemistry , Aldehydes/chemistry , Macrolides/chemistry , Molecular Structure , StereoisomerismABSTRACT
The first enantioselective total synthesis of the proposed structure of aldingenin B is reported in 16 steps from known compounds. The stereochemistry at C5 and C6 were established by an asymmetric acetal aldol. Following a ring-closing metathesis, a selective, substrate-controlled hydrogen bond-mediated dihydroxylation provided control of the C2 and C3 stereocenters. Discrepancies in the spectroscopic data of the synthetic and natural material led to the conclusion that the structure of the natural sample was misassigned.
Subject(s)
Sesquiterpenes/chemistry , Sesquiterpenes/chemical synthesis , Aldehydes/chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , StereoisomerismABSTRACT
The formal synthesis of (+)-sorangicin A was completed by two independent routes. Both approaches feature a cross metathesis reaction to form the C29-C30 bond to arrive at the bicyclic ether/tetrahydropyran fragment. Formation of the C15-C16 olefin to unite the dihydropyran fragment with the rest of the molecule was achieved by either a cross metathesis reaction or a Julia-Kocienski olefination.
Subject(s)
Aminoglycosides/chemical synthesis , Aminoglycosides/chemistry , Molecular Conformation , StereoisomerismABSTRACT
The total syntheses of (+)-vigulariol and (-)-sclerophytin A are reported in 15 steps and 16 steps, respectively, from a known compound. The flexible, readily scalable synthetic strategy allows for rapid construction of a critical tricyclic intermediate and is demonstrated via the synthesis of these two marine natural products. A key reaction in this synthetic protocol is a combination Wittig/intramolecular Diels-Alder cycloaddition.
Subject(s)
Bridged-Ring Compounds/chemical synthesis , Diterpenes/chemical synthesis , Ethers, Cyclic/chemical synthesis , Furans/chemical synthesis , Bridged-Ring Compounds/chemistry , Diterpenes/chemistry , Ethers, Cyclic/chemistry , Furans/chemistry , Molecular Conformation , StereoisomerismABSTRACT
The total synthesis of the originally proposed structure of briarellin J is reported in 15 steps from a known compound and in 23 steps from readily available materials. Key reactions include an exo-selective intramolecular Diels-Alder and a substrate-controlled hydroboration. Discrepancies in the spectroscopic data of the synthetic and natural material led to a revision of the assigned structure.
Subject(s)
Diterpenes/chemical synthesis , Crystallography, X-Ray , Ketones/chemical synthesis , Models, Molecular , Molecular StructureABSTRACT
The enantioselective total synthesis of spirofungins A (1) and B (2) is reported in 14 steps over the longest linear sequence. Key steps include the use of thiazolidinethione-mediated aldol reactions to assemble the major fragments and installation of the C1-C6 side chain using a cross metathesis reaction.
Subject(s)
Pyrans/chemical synthesis , Spiro Compounds/chemical synthesis , Aldehydes/chemical synthesis , Molecular Structure , Propanols/chemical synthesis , StereoisomerismABSTRACT
A convergent synthesis of the C31-C52 bis-tetrahydropyran core of the natural product amphidinol 3 is reported. A common intermediate was synthesized from d-tartaric acid utilizing an asymmetric glycolate alkylation/ring-closing metathesis sequence to construct the THP rings. Differential elaboration of the common intermediate allowed the synthesis of two distinct coupling partners which were joined through a modified Horner-Wadsworth-Emmons olefination to provide the bis-tetrahydropyran core.
Subject(s)
Alkenes/chemical synthesis , Biological Products/chemical synthesis , Pyrans/chemical synthesis , Alkenes/chemistry , Alkylation , Biological Products/chemistry , Dinoflagellida/chemistry , Marine Toxins/chemical synthesis , Molecular Structure , Oxocins/chemical synthesis , Pyrans/chemistry , Stereoisomerism , Tartrates/chemistryABSTRACT
Progress toward a highly convergent, asymmetric synthesis of brevenal is reported. Construction of the AB-ring and E-ring cyclic ether fragments was achieved through asymmetric alkylation/ring-closing metathesis strategies. A Horner-Wadsworth-Emmons olefination was used in a key bond-forming step to couple the advanced cyclic fragments and enable rapid access to the AB-E ring system.
Subject(s)
Ethers/chemical synthesis , Polymers/chemical synthesis , Alkylation , Catalysis , Dinoflagellida/chemistry , Ethers/chemistry , Ethers/pharmacology , Marine Toxins/isolation & purification , Marine Toxins/toxicity , Molecular Structure , Polymers/chemistry , Polymers/pharmacology , StereoisomerismABSTRACT
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.
Subject(s)
Ethers, Cyclic/chemical synthesis , Marine Toxins/chemical synthesis , Oxocins/chemical synthesis , Catalysis , Cyclization , Ethers, Cyclic/chemistry , Marine Toxins/chemistry , Molecular Structure , Oxocins/chemistry , StereoisomerismABSTRACT
The total synthesis of (+)-iriciniastatin A (psymberin) is reported in 19 steps and 6% overall yield. Key reactions include a highly convergent enolsilane-oxocarbenium ion union to generate the C8-C25 fragment and a late-stage coupling of a hemiaminal and acid chloride to complete the synthesis.
Subject(s)
Pyrones/chemical synthesis , Catalysis , Coumarins , Molecular Structure , Pyrones/chemistry , StereoisomerismABSTRACT
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.
Subject(s)
Ethers/chemical synthesis , Marine Toxins/chemical synthesis , Oxocins/chemical synthesis , Alkylation , Cyclization , Ethers/chemistry , Marine Toxins/chemistry , Molecular Structure , Oxocins/chemistry , Stereoisomerism , Structure-Activity RelationshipABSTRACT
The asymmetric total synthesis of pyranicin (1) is reported. The butenolide ring was constructed via an asymmetric alkylation/ring-closing metathesis strategy. The three stereocenters in the left-hand tetrahydropyran ring were installed by sequential chiral auxiliary-mediated aldol reactions. Closure of the tetrahydropyran and fusion of the alkyl backbone were affected via a sequential ring-closing metathesis-cross-metathesis strategy.
Subject(s)
Furans/chemical synthesis , Lactones/chemical synthesis , 4-Butyrolactone/analogs & derivatives , 4-Butyrolactone/chemical synthesis , 4-Butyrolactone/chemistry , Alkylation , Cyclization , Furans/chemistry , Lactones/chemistry , Molecular Structure , StereoisomerismABSTRACT
The enantioselective total synthesis of pironetin has been achieved in 11 steps from known aldehyde 2. The synthesis relies on the formation of 5 out of 6 stereocenters through titanium mediated iterative aldol reactions. Key steps in this synthesis include an acetal aldol reaction to establish the stereochemistry at C8 and C9, an acetate aldol reaction, and "Evans" syn aldol reaction.
Subject(s)
Aldehydes/chemistry , Pyrones/chemical synthesis , Thiazolidines/chemistry , Thiones/chemistry , Molecular Structure , Pyrones/chemistry , StereoisomerismABSTRACT
A highly convergent, enantioselective total synthesis of the potent antitumor agent apoptolidin A has been completed. The key transformations include highly selective glycosylations to attach the C27 disaccharide and the C9 6'-deoxy-l-glucose, a cross-metathesis to incorporate the C1-C10 trienoate unit, and a Yamaguchi macrolactonization to complete the macrocycle. Twelve stereocenters in the polypropionate segments and sugar units were established through diastereoselective chlorotitanium enolate aldol reactions.
Subject(s)
Antineoplastic Agents/chemical synthesis , Glucose/analogs & derivatives , Glucose/chemical synthesis , Macrolides/chemical synthesis , Pyrones/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Glucose/chemistry , Glycosylation , Macrolides/chemistry , Macrolides/pharmacology , Molecular Structure , Pyrones/chemistry , Pyrones/pharmacology , Stereoisomerism , Structure-Activity RelationshipABSTRACT
A total synthesis of brevetoxin A is reported. Two tetracyclic coupling partners, prepared from previously reported advanced fragments, were effectively united via a Horner-Wittig olefination. The resulting octacycle was progressed to substrates that were explored for reductive etherification, the success of which led to a penultimate tetraol intermediate. The tetraol was converted to the natural product through an expeditious selective oxidative process followed by methylenation.