Determination of the absolute configuration of the diterpene tonantzitlolone B

In this work synthetic and semi-synthetic studies toward the antitumor active natural product tonantzitlolone B are described, starting with an advanced intermediate obtained from the total synthesis of tonantzitlolone and a natural sample of this compound, respectively. The unknown absolute configuration of the stereogenic center in the side chain was elucidated to be (R).     

Verticilide: elucidation of absolute configuration and total synthesis

Verticilide (1) is a 24-membered cyclic depsipeptide isolated from the culture broth of Verticillium sp. FKI-1033. It inhibits ryanodine binding to ryanodine receptor (RyR) and has insecticidal activity. The stereochemistry of 2-hydroxyheptanoic acid in verticilide was elucidated by chiral HPLC analysis of the degradation product 6 and synthetic (+) and (-)-6. We also describe the practical total synthesis of verticilide. [reaction: see text].     

Total synthesis and absolute configuration of malyngamide W

A concise enantioselective synthesis of malyngamide W (1) and its 2'-epimer was described. The strategy was based on three key steps: (1) ozonolysis of compound 11 which was derived from (R)-(-)-carvone 8, followed by copper-iron-catalyzed rearrangement to give the key cyclohex-2-enone intermediate 5, (2) Nozaki-Hiyama-Kishi coupling reaction between aldehyde 4 and iodide 14 to afford alcohol 3, and (3) asymmetric (R)-CBS reduction of the ketone functionality in compound 21 to establish the C-2' chiral center in the target compound 1. The absolute configuration of malyngamide W (1) was thus confirmed via the synthesis of 1 and 2'-epi-1.     

Total synthesis and absolute configuration of nocardioazine B

The first total synthesis of the indole alkaloid nocardioazine B was accomplished in 10 steps with an overall yield of 11.8%, establishing the absolute stereochemistry of the natural product.     

Total synthesis of cyclic diterpene tonantzitlolone based on a highly stereoselective substrate-controlled aldol reaction and ring-closing metathesis

The total synthesis of the cyclic diterpene ent-tonantzitlolone (ent-1) is presented. Key steps for assembling the macrocyclic core structure of 1 are a highly selective aldol reaction and an E selective ring-closing metathesis reaction. A detailed investigation of these two steps and the final transformations towards the completion of the synthesis is disclosed.     

Total synthesis and the absolute configuration of citreoviral and citreoviridin

Both citreoviral and citreoviridin, metabolites of $\text{Penicillium citreo-viride}$ B., have been synthesized starting from D-glucose, in connection with which their absolute configuration has also been established.     

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.     

Total synthesis of amphidinolactone A and its absolute configuration

Asymmetric synthesis of amphidinolactone A, a cytotoxic macrolide from the cultured dinoflagellate Amphidinium sp., has been accomplished. Absolute configuration of amphidinolactone A was concluded to be 1 from comparison of the NMR data and [α]_D values of synthetic and natural amphidinolactone A.     

Total synthesis and determination of the absolute configuration of (+)-neoisoprelaurefucin

The first total synthesis of the seven-membered ring ether marine natural product (+)-neoisoprelaurefucin (1) has been achieved employing a regioselective internal alkylation of amide 3, a novel sequence for removal of the triethylsilyl group from the resulting triethylsilyloxepene 2, and a bromoetherification of alcohol 16 as key steps. In addition, the absolute stereochemistry of the natural product was assigned.     

Total synthesis and absolute configuration determination of (+)-subincanadine F

The first asymmetric synthesis of indole alkaloid (+)-subincanadine F was successfully accomplished with the uncommon 7-endo-trig stereoselective radical cyclization as the key step and its absolute configuration was thus assigned.     

Total synthesis and absolute configuration determination of (+)-bruguierol C

The first total synthesis and absolute configuration of bruguierol C are reported. The key step involved the diastereoselective capture of an in situ generated oxocarbenium ion via an intramolecular Friedel-Crafts alkylation.     

Total synthesis and absolute configuration of (-)-gummiferol

Stereoselective synthesis of two possible diastereomers of (-)-gummiferol was accomplished by the stepwise epoxidation and Cadiot-Chodkiewicz reaction as the key transformations. Detailed comparison of their (1)H and (13)C NMR data and specific rotation with those of the natural product led to the absolute structural elucidation of (-)-gummiferol.     

Total synthesis and determination of the absolute configuration of frondosin B.

Two concise syntheses of (+/-)-frondosin B (1), an interleukin-8 receptor antagonist, have been achieved from commercially available 5-methoxysalicylaldehyde. The seven-membered ring in ketone 33, the common intermediate for both syntheses, was built by a classical Friedel-Crafts reaction. The key step of the first route was facile cationic cyclization of the vinylogous benzofuran to the trisubstituted olefin (30 --> 16 + 38) to construct a six-membered carbocycle. Although this route demonstrated the efficacy of the stepwise approach to the frondosin ring-system, it also resulted in olefinic isomers that were easily isomerized in acidic conditions. In the second route, we utilized a Diels-Alder reaction between sterically demanding diene 42 and nitroethylene to fix the double bond in its required position in the resultant dimethylcyclohexane ring. A third total synthesis was devised for the purpose of determining the absolute configuration of frondosin B. It reached diene 42, this time in the enantiomerically defined form. From this point, naturally configured frondosin B was obtained in the enantiomerically enriched form. These studies establish the absolute configuration of the secondary methyl center in frondosin B to be R.     

Total synthesis of colombiasin A and determination of its absolute configuration

The total synthesis of the recently reported marine natural product colombiasin A (1) and determination of its absolute configuration are reported. Two Diels-Alder cycloadditions and a palladium-catalyzed rearrangement are employed as key reactions to construct the tetracyclic framework of the target molecule. The enantioselective synthesis of colombiasin A utilizes Mikami's [(S)-BINOL-TiCl2] catalyst to asymmetrically introduce the first chiral center during the initial Diels-Alder reaction and, in conjunction with X-ray crystallographic analysis of a bromine containing derivative, led to the assignment of the absolute configuration of the natural product.     

Total synthesis and determination of relative and absolute configuration of multiplolide A

A flexible approach for total syntheses of possible multiplolide A diastereomers establishing the relative and absolute configuration is documented. The adopted strategy features ring-closing metathesis (RCM) as the key reaction and screening of a set of substrates for the feasibility of RCM in general and for the requisite E-configuration of ring olefin in particular. Selective protecting groups manipulation prior to the assembly of the central macrocyclic core was instrumental in installing the epoxide functionality on a fully deprotected nonenolide at the end of the synthesis.