Feigrisolide C: structural revision and synthesis

[Carbohydrate structure: see text] The original macrodiolide structure proposed for feigrisolide C was incorrect. The true structure of feigrisolide C was identified as (2'S,3'S,6'R,8'R)-homononactoyl (2R,3R,6S,8S)-nonactic acid, which was confirmed by total synthesis.     

The first total synthesis of nakadomarin A

(-)-Nakadomarin A is a member of manzamine alkaloid isolated from a marine sponge and have a unique hexacyclic structure. The first total synthesis of (+)-nakadomarin A, an enantiomer of natural product, has been accomplished from stereochemically defined 4-oxopiperidin-3-carboxylic acid derivative. The synthesis established the structure of nakadomarin A including absolute configuration.     

天然产物goodyeroside A的全合成研究

以5-(S)-(d-盖氧基)-2(5H)-呋喃酮为起始原料．对具有肝保护活性的天然产物goodyeroside A进行了全合成研究。将合成所得目标产物的比旋光值及光谱数据与天然产物的数值相比较，两者一致，证明两者的结构与构型相同。     

Synthesis of the proposed structure of feigrisolide C

[reaction: see text] Possible structures of feigrisolide C were synthesized via ring-closing olefin metathesis reaction of a diester derivative prepared from 8-epi-nonactic acid, but physical characteristics of the synthetic samples did not match with those of the natural sample of feigrisolide C.     

The revised structure, total synthesis, and absolute configuration of streptophenazine A

A total synthesis of both diastereomers of the originally proposed structure for streptophenazine A (1) has been achieved. However, both synthetic compounds are different from the natural product. Re-examination of NMR data reported for streptophenazine A and a concise total synthesis of both diastereomers of 17 (17a and 17b) led to the structural revision of streptophenazine A to 17b. Asymmetric synthesis of (-)-streptophenazine A was also conducted, and its absolute configuration was determined to be 1'S,2'R.     

Total synthesis of unguisin A

The first synthesis of the γ-aminobutyric acid (GABA)-containing cyclic heptapeptide unguisin A is reported, confirming the structure of this natural product. Macrocyclization of a flexible GABA-containing linear precursor is found to proceed rapidly and in good yield.     

Synthetic Studies Concerned with the Proposed Structure of Ribisin F,a Compound with Nerve Growth Factor Potentiating Activity Isolated from the Medicinal Fungus Phellinus ribis

The synthesis of the enantiomer of the structure assigned to the title natural product has been achieved from abundant quinic acid. However, the NMR spectral data acquired on the synthetic material do not match those reported for ribisin F (which are of rather modest quality). In an effort to establish the true structure of ribisin F, an epimer of the assigned structure was also prepared from quinic acid. A comparison of the spectral data obtained on this epimer with those reported for the natural product proved a better match and based on optical rotation data the possible true structure of this distinctive, dihydroxylated and benzofuran-containing compound is tentatively proposed.     

Synthesis of reported and revised structures of amathamide D and synthesis of convolutamine F, H and lutamide A, C

Total synthesis of the published structure of amathamide D is described. Methyl 2,3,4-tribromo-5-hydroxybenzoate was selected as starting compound because it is readily accessible via acid-mediated Grob fragmentation-aromatization reaction of 1,4,5,6-tetrabromo-7,7-dimethoxybicyclo[2.2.1]hept-5-en-2-one. The aforementioned ester was transformed into the reported structure of amathamide D through methylation of a hydroxyl group and conversion of the ester moiety to a β-aminoethyl side chain. The NMR data of the synthetic compound did not conform to the reported natural product structure possessing contiguously positioned β-aminoethyl side chain, a set of three adjacent bromines, and a methyl ether linkage on the phenyl ring. This prompted us to redefine the natural product structure by synthesizing a product whose spectral data exactly matched with the reported data of amathamide D. The convolutamine H, with completely substituted phenyl ring adorned with an extra methyl ether functional group, has also been synthesized by application of Grob fragmentation-aromatization strategy to 3-(benzyloxy)-1,4,5,6-tetrabromo-7,7-dimethoxybicyclo[2.2.1]hept-5-en-2-one. This approach furnished directly methyl 2,3,4-tribromo-5,6-dimethoxybenzoate, which was converted straightforwardly into convolutamine H. Further, synthesis of convolutamine F and lutamide A and C is also described.     

Total synthesis of spiruchostatin B aided by an automated synthesizer

The total synthesis of a natural product HDAC inhibitor, spiruchostatin B, was successfully achieved. A 5-step synthesis that included an asymmetric aldol reaction was carried out in an automated synthesizer to provide an (E)-(S)-3-hydroxy-7-thio-4-heptenoic acid segment that is the crucial structure of cysteine-containing, depsipeptidic natural products such as spiruchostatins, FK228, FR901375, and largazole for their inhibitory activity against HDACs.     

WYE‐120318, a ring contraction product of methylnaltrexone,and structure revision of coniothyrione

A contracted ring degradation product, WYE‐120318 (compound 2), was discovered during the development phase for methylnaltrexone bromide (compound 1) drug substance. The compound was isolated by high‐performance liquid chromatography fractionation, and its structure was determined by spectroscopic data analyses. WYE‐120318 is formed from methylnaltrexone through a benzyl‐benzilic acid type rearrangement reaction to yield an α‐hydroxy‐cyclopentanecarboxylic acid substructure. The proposed structure and the formation mechanism are confirmed by the synthesis of WYE‐120318 from methylnaltrexone (compound 1). A similar benzyl‐benzilic acid type rearrangement reaction can be envisioned as the biological origin of remisporine A (compound 3), a naturally occurring cyclopentadienyl compound that autocatalytically dimerizes to remisporine B (compound 4). The structure of remisporine A was deduced from its dimer 4. Coniothyione (compound 5) can be considered as the first example of a stable natural product bearing the remisporine A skeleton. However, the regiochemistry of the chlorosubstitution in the coniothyrione structure needs to be revised to compound 6 on the basis of the nuclear magnetic resonance data and biogenesis analysis. Copyright © 2012 John Wiley & Sons, Ltd.     

A concise approach for the total synthesis of pseudolaric acid A

A new strategy for the stereoselective total synthesis of natural product pseudolaric acid A (1) was accomplished in 16 steps from commercially available starting material, featuring a samarium diiodide (SmI(2))-mediated intramolecular alkene-ketyl radical cyclization and a ring-closing metathesis (RCM) reaction to stereoselectively cast the unusual trans-fused [5-7]-bicyclic core of pseudolaric acid A (1).     

Synthesis of putative uniflorine A

A diastereoselective synthesis of the putative structure of the natural product uniflorine A has been achieved by using the Petasis borono-Mannich reaction and ring-closing metathesis as key steps. The NMR data of the synthetic material did not match that reported for the natural product. The structure of the final synthetic product was unequivocally determined by single-crystal X-ray study of its pentaacetate derivative. Thus it was concluded that the proposed structure of uniflorine A is incorrect.     

Concise enantiospecific, stereoselective syntheses of (+)-crispine A and its (-)-antipode

An enantiospecific and stereoselective total synthesis of the natural product (+)-crispine A has been demonstrated employing a Pictet-Spengler bis-cyclization reaction between commercially available (R)-(-)-methyl 2-amino-3-(3,4-dimethoxyphenyl)propanoate and 4-chloro-1,1-dimethoxybutane to preferentially provide the cis tricyclic adduct. Decarboxylation by a convenient two-step protocol provided the enantiopure natural product in three steps with an overall isolated yield of 32% from the amino acid. The unnatural antipode (-)-crispine A was similarly prepared in three steps from the commercially available (S)-(+)-amino acid.     

Total synthesis and structural confirmation of (±)-cuevaene A

The total synthesis and structural reassignment of cuevaene A have been completed. The key synthetic steps in the total synthesis included a base-promoted double conjugate addition and further elaboration to generate the tricyclic core structure, followed by construction of the trienoic acid side chain. Detailed comparison of proton and carbon NMR data with published values enabled the connectivity of the natural product, which had been debated in earlier publications, to be confirmed.     

A (-)-sparteine-directed highly enantioselective synthesis of boroproline. Solid- and solution-state structure and properties

A two-step, direct asymmetric synthesis of the trifluoroacetate ammonium salt of boroproline is reported. (-)-Sparteine-mediated lithiation of N-Boc-pyrrolidine afforded N-Boc-aminoboronic acid in good yield and enantioselectivity as determined by HPLC (pinanediol ester). Deprotection using TFA yielded the ammonium salt; full characterization data are presented, and the structure in aqueous solution and the occurrence of a B-N species are discussed.     

Total synthesis and correct absolute configuration of malyngamide U

The enantioselective synthesis of the previously proposed structure of malyngamide U (1) was accomplished in 18 steps from (S)-(+)-carvone. The key steps involved a hydroxymethylation of (S)-(+)-carvone and an asymmetric Henry reaction of aldehyde (+)-5, as well as condensation with the acid 3. The 1H and 13C NMR data of the synthetic compound 1 were not consistent with the data of the reported malyngamide U. The C-2' epimer of compound 1 was therefore synthesized by a similar reaction sequence. While the NMR data of C-2' epimer 23 were in full agreement with those of the reported product, the discrepancy in the specific rotation data suggested the correct structure of malyngamide U should be structure 2, in which the absolute configuration of the amine part was enantiomeric with that in compound 23. Then the correct absolute configuration of revised malyngamide U (2) was confirmed by the similar synthesis from (R)-(-)-carvone.     

Synthesis of the enantiomer of the structure assigned to the natural product nobilisitine A

The synthesis of the enantiomer of the structure, 1, assigned to the natural product nobilisitine A has been accomplished using the enantiomerically pure cis-1,2-dihydrocatechol 4 as starting material. The (1)H and (13)C NMR spectral data derived from compound ent-1 do not match those reported for the natural product, thus suggesting its structure has been incorrectly assigned.     

N-methoxy-N-acylnitrenium ions: application to the formal synthesis of (-)-TAN1251A

[structure: see text]. A formal synthesis of the muscarinic M(1) receptor antagonist (-)-TAN1251A (7) from L-tyrosine is described. Central to this venture has been the construction of the 1-azaspiro[4.5]decane skeleton present in the natural product by an N-methoxy-N-acylnitrenium ion-induced spirocyclization. The dienone generated in this transformation, 10, was converted to (-)-TAN1251A via tricycle 9, an intermediate in Kawahara's recent synthesis of racemic 7.     

Stereocontrolled synthesis of the A/B-ring fragment of gambieric acid B: reassignment of the absolute configuration of the polycyclic ether region

Stereocontrolled synthesis of the A/B-ring fragment of the originally assigned structure of gambieric acid B and its possible diastereomers has been accomplished. Detailed comparison of their 1H and 13C NMR data with those of the corresponding moiety of the natural product culminated in a stereochemical reassignment of the absolute configuration of the polycyclic ether region of gambieric acid B.