Total synthesis of (+/-)-psychotrimine

new process for the union of anilines with tryptamine derivatives has been developed, furnishing C-3 quaternized pyrroloindoline architectures. This chemoselective coupling of a tryptamine with 1.2 equiv of 2-iodoaniline proceeds efficiently on a gram-scale using only the simple reagents N-iodosuccinimide and triethylamine. Using this new reaction, the complex natural product psychotrimine has been fashioned with a rare level of efficiency and practicality. From a readily available bromotryptamine, only four steps (41-45% overall isolated yield) are necessary to procure gram quantities of the natural product. Functional group manipulations, protecting group chemistry, and unnecessary redox fluctuations have been minimized.     

Total synthesis of (-)-tirandamycin C

Tirandamycin C is a newly isolated member of the tetramic acid family natural products. We described herein the first enantioselective synthesis of natural (-)-tirandamycin C, the postulated biosynthetic precursor of other members of this family. The highly stereoselective (>15:1) mismatched double asymmetric γ-stannylcrotylboration reaction of aldehyde 8 with crotylborane reagent (R)-E-9 was utilized to access the key anti,anti-stereotriad 18.     

Formal synthesis of (±)-cladoniamide G

The formal synthesis of (±)-cladoniamide G, a natural product that exhibits cytotoxicity against human breast cancer MCF-7 cells, is presented. Our strategy employed a Suzuki–Miyaura coupling to join the two indole subunits of this natural product.     

(一)-莪术二酮的全合成

(+)-莪术二酮系从中药温莪术中分到的抗癌活性成份. 本文研究了由(-)-香芹酮经12步反应合成(-)-莪术二酮的过程, 并以此结果证实了天然(+)-莪术二酮的绝对构型.     

Total synthesis of (+/-)-mersicarpine

The first total synthesis of the indole alkaloid mersicarpine is reported. Key steps include a beta-dicarbonyl radical cyclization, as well as an oxidation of the benzopyrrole moiety to establish the masked 1,2-dicarbonyl functionality. An X-ray crystal structure and discussion of the 1H NMR behavior of the natural product are also presented.     

A total synthesis of (±)-dihydropalustrine

Dihydropalustrine has been synthesized by a β-lactam-imino ether coupling route. A dehydro precursor previously considered to represent palustrine has now been shown to be nonidentical with the natural product.     

Total synthesis of (+/-) tanikolide

The natural polyketide (+/-)-tanikolide (1) was prepared in eight steps starting from hex-5-enol. Key steps in this synthesis are a Sharpless dihydroxylation and a Grignard reaction between an alkyl halogenide and a ketone. The lactonization occurred spontaneously during the oxidation of the primary alcohol function to the carboxy group.     

Biomimetic synthesis and structural revision of (+/-)-tridachiahydropyrone

A short synthesis of the revised structure of the marine natural product tridachiahydropyrone is described. A novel biomimetic photochemical electrocyclization was employed to construct the bicyclic carbon framework from an open-chain polyene precursor. The spectroscopic data matched that of the isolated natural product, supporting a revised structure of this complex metabolite.     

Total synthesis of (+/-)-dysibetaine

The marine natural product dysibetaine was synthesized in racemic form from a levulinic acid derivative using a convertible isocyanide and an ammonium acetate in the Ugi 4-center-3-component condensation reaction.     

Total synthesis of (-)-dysithiazolamide

The tetrachlorinated natural product (-)-dysithiazolamide was synthesized from l-glutamic acid in a convergent way, confirming the previously proposed (2S,4S,6S,8S) absolute stereochemistry.     

Concise asymmetric synthesis of (-)-sparteine

A six-step asymmetric synthesis of natural (-)-sparteine from ethyl 7-iodohept-2-enoate is reported, involving a connective Michael addition of an amino ester-derived enolate to an alpha,beta-unsaturated amino ester.     

Total synthesis of (-)- and (+)-dysibetaine

Glycidamides 6R and 6S were elaborated to (R,R)- and (S,S)-dysibetaines (1R and 1S) by intramolecular alkylation and functional group modification in 23% overall yield. The absolute stereochemistry of natural dysibetaine was established as S,S by comparison of the optical rotation of the natural product with that of the synthetic materials.     

Total synthesis of (-)-anamarine

Total synthesis of polyhydroxy δ-pyranone natural product (-)-anamarine is accomplished from D-(-)-tartaric acid. The main feature of the synthesis is the utility of hitherto unexplored β-keto phosphonate derived from tartaric acid amide and further elaboration involving stereoselective reduction.     

Total synthesis of (+/-)-frondosin B

An expeditious reaction sequence featuring a microwave-assisted tandem 5-exo cyclization-Claisen rearrangement process was used to assemble the A/B ring system of frondosin B. Completion of the target natural product was achieved in 38.2% yield over an eight-step linear sequence.     

Total synthesis of (-)-dactylolide and formal synthesis of (-)-zampanolide via target oriented beta-C-glycoside formation

The total synthesis of (-)-dactylolide and formal synthesis of (-)-zampanolide via target oriented beta-C-glycoside formation is described. The two key reactions involved a stereoselective reduction of the appropriate oxocarbenium cation and a highly chemo- and diastereoselective ring-closing metathesis protocol for the formation of the macrocyclic core. In addition to the described chemistry, in vitro screening of the antipode of natural dactylolide against the NCI's 60 cancer cell line helped to illuminate the critical importance of the N-acyl hemiaminal side chain of natural zampanolide for its reported potent nanomolar cytotoxicities. Furthermore, by means of the in vitro screen of (-)-dactylolide, a promising cancer therapeutic lead has now emerged for a variety of carcinomas. More specifically, (-)-dactylolide exhibited GI50 values in the nanomolar (25-99 ng/mL) range against the four cell lines HL-60, K-562, HCC-2998, and SF-539, while displaying modest LC50 values.     

Total synthesis of (-)-isoschizogamine

A first asymmetric total synthesis of (-)-isoschizogamine has been accomplished. Our synthesis features the facile construction of the carbon framework of the natural product through a Wagner-Meerwein rearrangement, a tandem metathesis, a stereoselective rhodium-mediated 1,4-addition of an arylboronic acid, and a ring-closing metathesis via a hemiaminal ether.     

Total synthesis of (-)-callystatin A

A total synthesis of the cytotoxic polyketide marine natural product callystatin A is described. The route features chiral allenylmetal additions to construct the polypropionate C15-22 segment and an sp(2)-sp(3) Suzuki coupling to join the C1-C11 and C12-C22 subunits.     

Total synthesis of (+/-)-paeonilide

The total synthesis of paeonilide, a natural anti-PAF (platelet-activating factor) new skeleton monoterpenoid with an IC(50) value of 8 microg/mL, was achieved in 16 steps with 15% overall yield from commercially available 2-hydroxy-4-methylacetophenone. [reaction: see text]     

Total synthesis of (-)-reveromycin B

[structure: see text] The total synthesis of the epidermal growth factor inhibitor reveromycin B (2) is described. A novel, convergent, and stereoselective reaction sequence was utilized to construct the 5,6-spiroketal system 10 which was converted into the natural product 2 by a 16-step sequence.     

Total synthesis of (S)-(−)-cyclooroidin

The first total synthesis of enantiopure (S)-(−)-cyclooroidin is described. Absolute configuration of this natural product has been confirmed by comparison of the optical rotation value of our synthetic sample with the one measured on natural cyclooroidin.