First stereoselective synthesis of synargentolide A and revision of absolute stereochemistry

The first stereoselective total synthesis of synargentolide A isolated from Syncolostemon argenteus has been achieved from commercially available (R)-benzyl glycidyl ether using Sharpless asymmetric epoxidation and cross-metathesis reactions as the key steps. Comparing the spectral data of the synthesized and naturally occurring synargentolide A, the C4′ and C6′- stereogenic centers of the natural synargentolide A were assigned a corrected anti relationship.     

Total synthesis and absolute stereochemistry of plakortone D

The first total synthesis of plakortone D is described and thereby establishes the structure and absolute stereochemistry of the most biologically active member of the marine-derived plakortone family. The sterically congested bicyclic lactone core results from a Pd(II)-induced hydroxycyclization-carbonylation-lactonization sequence on an enediol whose chirality was installed by AD-technology. Attachment of the side chain, also constructed using AD-methodology, was achieved by using a modified Julia coupling. The described approach enables acquisition of other plakortones and analogues, in the correct (natural) stereochemical series.     

Total synthesis and absolute stereochemistry of plakortone E

The absolute stereochemistry of plakortone E, a cytotoxic metabolite of the Caribbean sponge, was established to be 1, by the synthesis of the racemic C-8 epimer (±)-2 and then of (−)-1 itself, which was identical with the natural compound.     

A stereoselective synthesis of verbalactone—determination of absolute stereochemistry

A total synthesis of verbalactone has been achieved starting from l-malic acid. The two appropriately protected acid and alcohol segments were prepared from l-malic acid and lactonized under Yamaguchi conditions.     

Total synthesis and revision of stereochemistry of the marine metabolite trunkamide A

The isolation of the cytotoxic Lissoclinum sp. metabolite trunkamide A was reported in 1996. After completion of a total synthesis in 1999, it became clear that the structure of this marine natural product had to be revised. We now report the first preparation of actual trunkamide A in a total synthesis that serves as an unambiguous structural and stereochemical proof. Highlights of our synthetic strategy are a Lewis acid assisted aziridine opening that was used for the preparation of the novel reverse-prenylated serine and threonine side chains as well as an efficient oxazoline-thiazoline interconversion on the macrocyclic skeleton. In addition, several stereoisomers prepared by complementary synthetic protocols serve to illustrate the general scope of our methodology and confirm the configurational assignment.     

Total synthesis of amaminol A: establishment of the absolute stereochemistry

The first synthetic route to amaminol A with use of an organocatalytic intramolecular Diels-Alder reaction is reported. The absolute stereochemistry is proven with a crystallographic image of a cyclic carbamate of amaminol A.     

Asymmetric total synthesis and absolute stereochemistry of the neuroactive marine macrolide palmyrolide A

The first asymmetric total synthesis and determination of the absolute configuration for the neuroactive marine macrolide palmyrolide A is described. The highlight of the synthesis is macrocyclization via trans-enamide formation catalyzed by copper(I) iodide and cesium carbonate. Comparison with the authentic spectral data confirms the synthesis of (+)-ent-palmyrolide A.     

Radicamines A and B: synthesis and revision of the absolute configuration

[reaction: see text] Starting from D-xylose, enantioselective syntheses of 1 and 2, the proposed structures for radicamines A and B, were accomplished. Both (1)H and (13)C NMR spectra of 1 and 2 were identical with those of the natural products, but the optical rotation measurements identified that 1 and 2 were actually the enantiomers of the natural radicamines A and B, respectively.     

First enantioselective synthesis and absolute stereochemistry assignment of new monocyclic sesquiterpenes from Artemisia chamaemelifolia

We herein report the first enantioselective synthesis of two new monocyclic sesquiterpenes from Artemisia chamaemelifolia starting from an enantiopure building block. The key feature of the present approach is to allow complete control of all the stereogenic centers present in the natural products and to elucidate their absolute stereochemistry, which to date is unknown.     

Asymmetric synthesis of (+)-geranyllinaloisocyanide: assignment of absolute stereochemistry

The first nonracemic synthesis of (+)-geranyllinaloisocyanide, starting with (-)-lactic acid methyl ester, has been accomplished by exploiting a [3.3] sigmatropic rearrangement of allyl cyanate. The synthesis enables assignment of the S configuration of the C(3) isocyano substituted, quaternary stereogenic center in natural geranyllinaloisocyanide.     

Asymmetric total synthesis and revision of absolute configurations of azaphilone derivative felinone A

The first total synthesis of the azaphilone derivative, felinone A, was accomplished. The absolute configuration of natural felinone A was revised to be 3S, 6S, and 7R.     

Biomimetic synthesis and proposal of relative and absolute stereochemistry of heronapyrrole C

The first synthesis of (-)-heronapyrrole C, the enantiomer of a unique farnesylated 2-nitropyrrole natural product is described. With none of the chiral centers of heronapyrrole C originally assigned, we proposed the most likely natural configuration on the basis of a putative biosynthetic pathway. The key step of the synthesis is a biomimetic polyepoxide cyclization cascade to establish the bis-THF moiety. Thus, (-)-heronapyrrole C is synthesized in eight steps from commercially available starting materials.     

Stereoselective synthesis of (+)-cerulenin from d-glucose

(+)-Cerulenin $\text{1a}$ was synthesized stereoselectively from D-glucose.     

Total synthesis of (+)-FR-900493 and establishment of its absolute stereochemistry

The first total synthesis of (+)-FR-900493, an antibacterial nucleoside antibiotic possessing a 6′-N-alkyl-5′-O-aminoribosyl-glycyluridine structure, is described, and its relative and absolute stereochemistries were established. Key elements of the approach include the early-stage introduction of the aminoribose moiety and two sequential reductive alkylations of an amino group at the 6′-position. This synthetic strategy could be applicable to the synthesis of related nucleoside antibiotics, such as the more potent antibacterial nucleoside antibiotics, muraymycins.     

Total synthesis and revision of C6 stereochemistry of (+)-amphidinolide W

An enantioselective first total synthesis and structural revision of the cytotoxic natural product amphidinolide W is described. We initially investigated a ring-closing metathesis based synthetic strategy to form the 12-membered macrocycle. This strategy was unsuccessful as it led to formation of a 17-membered macrocycle. Subsequently, we explored an alternative strategy that involved cross-metathesis followed by a Yamaguchi macrolactonization reaction sequence utilizing the same key intermediates. This strategy led to the synthesis of amphidinolide W. The synthesis was carried out in a convergent manner, and four of the five stereogenic centers in amphidinolide W were set by asymmetric synthesis. The synthesis features Sharpless asymmetric dihydroxylation, diastereoselective alkylation, efficient cross-metathesis of functionalized substrates, and novel functional group transformations using selective lipase-catalyzed hydrolysis of the primary acetate group. Of particular note, the C6 absolute stereochemistry of amphidinolide W has now been revised through our synthesis.     

Assignment of absolute stereochemistry and total synthesis of (-)-spongidepsin

[structure: see text] An enantioselective total synthesis of (-)-spongidepsin (2) and elucidation of the absolute stereochemistry of its four stereocenters are described. Spongidepsin (2), a 13-membered depsipeptide isolated from the Vanuatu marine sponge Spongia sp., has shown potent antitumor properties against a variety of NCI tumor cell lines. Our synthesis is convergent, and the absolute stereochemistry of four of the five chiral centers was assigned through synthesis.     

First asymmetric total synthesis of (+)-steganacin determination of absolute stereochemistry

(+)-Steganacin was synthesized in a new and highly specific asymmetric pathway based on the novel application of chiral γ-lactone as a chiral synthon. By this synthesis the absolute stereochemistry of natural (?)-steganacin could be determined in unequivocal way.