Total syntheses of the proposed structures of cuevaene A

Two proposed structures of cuevaene A were synthesized and the NMR spectra of both structures are proved to be inconsistent with those of the natural product. The structure of cuevaene A is still unclear and needs to be revised.     

Synthesis and structure of tolyporphin A O,O-diacetate

[formula: see text] The revised structure of tolyporphin A O,O-diacetate (2b) was synthesized by assembling fragments 4, 5, and 12. The synthetic substance was found to be identical to the O,O-diacetate derived from natural tolyporphin A in every respect, thus establishing the relative and absolute configurations of this natural product.     

Synthesis of the reported structure of the bisbenzoquinone lanciaquinone, isolated from Maesa lanceolata

Lanciaquinone, isolated from Maesa lanceolata, was originally assigned as a bisbenzoquinone with a C14-chain linking the two quinone rings. A synthesis of the reported structure, in which the key step is a double Claisen rearrangement, suggests that the structure of the natural product needs to be revised.     

Asymmetric total synthesis of reported structure of eudistomidin B, an indole alkaloid isolated from a marine tunicate

Eudistomidin B, isolated from a marine tunicate, was originally assigned a tetrahydro-β-carboline structure with a 2-p-tolylethanamine residue. Asymmetric total synthesis of the reported structure of natural product, which features an intramolecular diastereoselective Pictet-Spengler cyclization, suggests that the reported structure of the natural product needs to be revised.     

A total synthesis prompts the structure revision of haouamine B

A concise asymmetric approach to the indeno-tetrahydropyridine core of the unusual alkaloid haouamine B allowed for an investigation of a biomimetic oxidative phenol coupling as a proposed biosynthetic step, and ultimately provided access to the published structure of the natural product. As a consequence of our synthetic studies, the structure of haouamine B has been revised.     

Lasonolide A: structural revision and total synthesis

The proposed structure of lasonolide A was synthesized employing radical cyclization reactions of beta-alkoxyacrylates for preparation of the tetrahydropyranyl units A and B, but the spectroscopic data did not match those of the natural product. Both enantiomers of a revised structure featuring 17E,25Z double bonds were synthesized, and the (-)-isomer was found to be the biologically active enantiomer.     

Total synthesis of indole-3-acetonitrile-4-methoxy-2-C-β-D-glucopyranoside. Proposal for structural revision of the natural product

Indole-3-acetonitrile-4-methoxy-2-C-β-D-glucopyranoside (1), a novel C-glycoside from Isatis indigotica with important cytotoxic activity, has been prepared in ten steps from ethynyl-β-C-glycoside 3 and 2-iodo-3-nitrophenyl acetate 6. Key steps in the synthesis include a Sonogashira coupling and a CuI-mediated indole formation. NMR spectroscopic data for synthetic 1 differs from that reported for the natural product. A revised structure for the natural product, containing an alternate carbohydrate substituent, is proposed.     

Total synthesis of dipiperamide A and revision of stereochemical assignment

The first total synthesis of dipiperamide A has been achieved by employing a solid-state photodimerization of an (E)-cinnamic acid derivative. This critical step results in the cyclobutane ring, which exists in the natural product, with full control of the regio- and stereochemistry at the four stereogenic centers. Results from these studies indicate that the proposed stereostructure of natural dipiperamide A should be revised to the structure originally assigned to dipiperamide B.     

Total synthesis of the proposed structure of brevenal

Total synthesis of the proposed structure of brevenal, a natural marine polycyclic ether product, has been accomplished. The synthesis features (i) convergent synthesis of the pentacyclic polyether skeleton using our developed Suzuki-Miyaura coupling strategy and (ii) construction of the multi-substituted dienal side chain by CuTC-mediated Stille reaction. Comparison of the NMR data of the synthetic compound with those reported for the natural product revealed that the proposed structure of brevenal needs to be revised.     

Synthesis of the alleged structure of sclerophytin A. The setting of two oxygen bridges within the fused cyclodecanol B ring is not Nature's Way

[reaction: see text] The structure attributed to sclerophytin A, a cytotoxic soft coral metabolite, was synthesized in an enantioselective manner from (5S)-5-(d-menthyloxy)-2(5H)-furanone. The spectral properties and polarity of the synthetic product require that the structural assignment to the natural material be revised.     

The pursuit of palau'amine

Since its discovery in 1993, the marine natural product palau'amine has intrigued natural product chemists. Its exotic molecular architecture and purported bioactivity made it an ideal target for synthesis. However, as the years went by and related marine alkaloids were isolated, a skeptical eye was cast on the structure of palau'amine; recently these suspicions were confirmed and the structure of palau'amine revised. This Minireview gives a careful overview of the structural revision and its ramifications to both its biogenesis and total synthesis.     

Total synthesis, structure revision, and absolute configuration of (-)-brevenal

Total synthesis of structure 1 originally proposed for brevenal, a nontoxic polycyclic ether natural product isolated from the Florida red tide dinoflagellate, Karenia brevis, was accomplished. The key features of the synthesis involved (i) convergent assembly of the pentacyclic polyether skeleton based on our developed Suzuki-Miyaura coupling chemistry and (ii) stereoselective construction of the multi-substituted (E,E)-dienal side chain by using copper(I) thiophen-2-carboxylate (CuTC)-promoted modified Stille coupling. The disparity of NMR spectra between the synthetic material and the natural product required a revision of the proposed structure. Detailed spectroscopic comparison of synthetic 1 with natural brevenal, coupled with the postulated biosynthetic pathway for marine polyether natural products, suggested that the natural product was most likely represented by 2, the C26 epimer of the proposed structure 1. The revised structure was finally validated by completing the first total synthesis of (-)-2, which also unambiguously established the absolute configuration of the natural product.     

Synthesis and Stereochemical Revision of the C31–C67 Fragment of Amphidinol 3

Amphidinol 3 (AM3) is a marine natural product produced by the dinoflagellate Amphidinium klebsii. Although the absolute configuration of AM3 was determined in 1999 by extensive NMR analysis and degradation of the natural product, it was a daunting task because of the presence of numerous stereogenic centers on the acyclic carbon chain and the limited availability from natural sources. Thereafter, revisions of the absolute configurations at C2 and C51 were reported in 2008 and 2013, respectively. Reported herein is the revised absolute configuration of AM3: 32S, 33R, 34S, 35S, 36S, and 38S based on the chemical synthesis of partial structures corresponding to the C31–C67 fragment of AM3 in combination with degradation of the natural product. The revised structure is unique in that both antipodal tetrahydropyran counterparts exist on a single carbon chain. The structural revision of AM3 may affect proposed structures of congeners related to the amphidinols.     

Synthesis and structure revision of the coumarin, celerin

The four possible structures (2, 4, 6 and 8) for celerin have been synthesised and the structure of the natural product revised to 8-hydroxy-7-methoxy-5-(1,1-dimethylallyl) coumarin (8).     

Synthesis and revision of stereochemistry of rubescensin S

An effective two step transformation of oridonin to 15,16-seco-ent-kaurane skeleton is reported. We also achieved the conversion of one intermediate to natural product rubescensin S and revised its structure as a 13S configuration although 13R is reported in the literature.     

Structure revision of plakotenin based on computational investigation of transition states and spectroscopic properties

We show that the previously [Tetrahedron Lett.1992, 33, 2579] proposed structure of natural plakotenin must be revised. Recently, the total synthesis of plakotenin was achieved via an intramolecular Diels-Alder reaction from a (E,E,Z,E)-tetraene as linear precursor. Using density functional theory, the computation of the four possible transition states for this reaction shows that the previously proposed structure could only have been formed via an energetically high-lying transition state, which is very unlikely. Instead, we suggest that the structure of plakotenin corresponds to the product formed via the lowest transition state. A comparison of experimental and theoretical optical rotation, circular dichroism, and two-dimensional nuclear Overhauser enhancement spectra conclusively proves that the structure of plakotenin is the one that is suggested by the transition state computations. Moreover, the simulation of the nuclear Overhauser enhancement spectra suggests that it is most likely that the misassignment of the (1)H chemical shifts of two methyl groups has led to the wrong structure prediction in the 1992 work. The previously proposed structure of iso-plakotenin remains unaffected by our structure revision, but the structures of homo- and nor-plakotenin must also be revised. The present work shows how the total synthesis of a natural product, together with the theoretical determination of the barrier heights of the reactions involved, can be of great help to assign its structure. It appears that intramolecular Diels-Alder reactions can be modeled accurately by today's first-principles methods of quantum chemistry.     

Claisen rearrangements-XV : structure revision of the coumarin, celerin, by synthesis

The four possible structures, 9,12,17 and 26 for celerin have been synthesised and the structure of the natural product revised to8-hydroxy-7-methoxy-5-(l,l-dimethylallyl) coumarin 26. Efficient alternative synthetic routes to sibiricol 5, coumurrayin 6 and pinnarin 13 have been established.     

A new synthetic method of 3-acyltetronic acid derivatives and its application to the synthesis of isoaspertetronin a (isogregatin A)

A new synthetic method of 3-acyltetronic acid derivatives from the corresponding 3-bromo compound via lithiation with n-BuLi followed either by acylation with acid chloride or better by first reacting with aldehyde and then subsequent oxidation with active MnO₂ is described. A revised structure $\text{10}$ for aspertetronin A(gregatin A) was presented based on the synthesis of the proposed structure $\text{8}$ and spectral comparison of a model compound $\text{12}$ with the natural product.     

Total synthesis of 1-deoxygulonojirimycin. Revision of the absolute configuration of the natural product

A concise, stereoselective synthesis of 1-deoxygulonojirimycin was achieved and the absolute configuration of the natural product was revised. Key features involve diastereoselective oxazoline formation catalyzed by palladium(0), RCM and dihydroxylation.     

Synthesis of amorphane and cadinane sesquiterpenes from fabiana imbricata

The monoterpene (−)-isopulegol (7) has been used as a starting material for the total synthesis in eight/nine steps of two sesquiterpenes which were recently isolated from the medicinal plant Fabiana imbricata. Use of this approach has shown that a structure proposed as 3,11-amorphadiene (3) should be revised to that of 4,11-cadinadiene (18) and confirmed the structure proposed for the natural product 4-amorphen-1 1-ol (1).