Concise total synthesis of (+)-crocacin C

The cytotoxic natural product (+)-crocacin C ( 1) has been synthesized in 10 linear steps from commercially available Evans' chiral propionimide in 5% overall yield (8 steps from Evans' chiral dipropionate synthon). No protecting groups were utilized.     

Concise total synthesis of (+)-carpamic acid

We report herein an efficient enantioselective synthesis of (+)-carpamic acid, with nine steps as the longest linear sequence, the key strategy being based on a novel sequence of a cross-metathesis (CM) reaction and a subsequent cyclizing reductive amination to form the piperidine ring.     

The lyconadins: enantioselective total syntheses of (+)-lyconadin A and (-)-lyconadin B

A full account of the enantioselective total syntheses of (+)-lyconadin A (1) and (-)-lyconadin B (2) is presented. Central to this venture was recognition and deployment of a key strategy-level intramolecular aldol/conjugate addition cascade that led, in a single operation, to two new carbon-carbon sigma-bonds, three new stereogenic centers, and two new rings, albeit with the incorrect stereogenicity at C(12) for the lyconadins. Correction of the C(12) stereogenicity was achieved via innovative use of a protonated intramolecular aminal. An aminoiodo olefin cyclization, in conjunction with alpha-pyridinone and 3,4-dihydropyridinone annulation protocols, permitted completion of the syntheses of (+)-lyconadin A (1) and (-)-lyconadin B (2), respectively.     

Concise total synthesis of (+)-brefeldin A: a combined beta-lactone/cross-metathesis-based strategy

[reaction: see text] A highly convergent total synthesis of (+)-brefeldin A that relies on a diastereoselective, beta-lactone-based cyclopentane synthesis combined with complex cross-metathesis reactions is described. The utility of beta-lactones for natural product synthesis and the versatility of cross-metathesis in this context were demonstrated, including the tolerance of an epimerizable aldehyde and a beta-lactone.     

Concise formal synthesis of (+)-neopeltolide

A concise formal synthesis of (+)-neopeltolide (1) has been accomplished. The synthesis demonstrated high atom efficiency employing only one step of functional group protection. Key steps involved iridium-catalyzed double asymmetric carbonyl allylation, palladium-catalyzed intramolecular alkoxycarbonylation, ruthenium-catalyzed olefin isomerization, and ring-closing metathesis.     

Concise synthesis of (+)-serinolamide A

Serinolamide A, isolated from a species of marine cyanobacteria, exhibits a moderate agonist effect and selectivity for the CB₁ cannabinoid receptor, which is unusual for marine natural products. Herein, we reported a highly efficient enantiospecific first total synthesis of (+)-serinolamide A from l-serine in nine steps with 30% overall yield. The synthesis method provides a facile, practicable, and economical approach for the preparation of other similar endocanabinoid lipids.     

Concise formal synthesis of (+)-pyripyropene A

A concise enantioselective synthesis of A/B bicyclic segment of naturally occurring α-pyrone meroterpenoid pyripyropene A is achieved in 9 steps (LLS) and 7.5% yield starting from R-(?)-carvone. The significant points of the synthesis include: (1) an intramolecular 1, 3-dipolar cycloaddition reaction to construct the A ring and assemble C4 quaternary carbon stereocenter as well; (2) reductive cleavage of the oxazole motif utilized Raney Ni/B(OCH₃)₃.     

Concise asymmetric total synthesis of obolactone

The first efficient asymmetric synthesis of obolactone 1 has been accomplished in 11 steps and with a 15% overall yield in which Brown's enantioselective allylation reactions and ring-closing metathesis reaction are key steps.     

A total synthesis of (+)-brefeldin a

A key intermediate, a substituted cyclopentanonitrile ($\text{10}$) with correct stereochemistry, was prepared from D-mannitol and converted to the Corey's intermediate ($\text{27}$) without a C₁₅-epimer, which was finally transformed to (+)-brefeldin A.     

Concise total synthesis of (+/-)-maritidine

[reaction: see text] Maritidine can be readily obtained from the corresponding protected beta,gamma-unsaturated ketone. The quaternary carbon of maritidine was created for the first time via an intramolecular Heck reaction.     

Concise total synthesis of calothrixins A and B

The concise total synthesis of calothrixins A and B has been accomplished by utilizing the one-pot formation of hexatriene as a key intermediate via the palladium-catalyzed tandem cyclization/cross-coupling reaction of triethyl(indol-2-yl)borate. In another key transformation, the indolo[3,2-j]phenanthridine core was prepared in high yield via Cu(I)-mediated 6π-electrocyclization.     

Concise total synthesis of phidianidine A and B

The shortest total synthesis of cytotoxic indole alkaloids phidianidine A and B is described. Rapid assembly of the 1,2,4-oxadiazole core from a novel N-hydroxyguanidine and the corresponding indole-3-acetic acid chloride led to formal syntheses of phidianidine A and B in only three steps from known compounds. Deprotection under standard conditions provided the trifluoroacetate salts of phidianidine A and B in quantitative yield.     

Concise total synthesis of (-)-mersicarpine

A concise total synthesis of (-)-mersicarpine from a known cyclohexanone was accomplished. The azepinoindole core was constructed by a DIBAL-H-mediated reductive ring-expansion reaction of oxime.     

Concise asymmetric total synthesis of 9-epi-sessilifoliamide J

A 10-step asymmetric synthesis of 9-epi-sessilifoliamide J (20), together with sessilifoliamide J (6), has been accomplished from the key chiral building block 11 via a threo-selective vinylogous Mannich reaction and a Ley oxidation-SmI(2)-mediated coupling lactonization. The absolute configuration of the natural sessilifoliamide J was established.     

Concise enantioselective total syntheses of (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine and (+)-norchelidonine by a Pd II-catalyzed ring-opening strategy

New enantioselective syntheses of the B/C hexahydrobenzo[c]phenanthridine alkaloids (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine, and (+)-norchelidonine are described. Our rapid and convergent route to this class of natural products involved the development and application of a Pd II-catalyzed asymmetric ring-opening reaction of a meso-azabicyclic alkene with an aryl boronic acid as the key step. By screening a variety of functionalized ortho-substituted aryl boronic acids, chiral ligands and reaction conditions we were able to prepare the requisite cis-1-amino-2-aryldihydronaphthalenes in high yield and in up to 90 % ee. Early attempts to complete the synthesis of (+)-homochelidonine using an N-Boc azabicyclic alkene are described in full. The successful route required a protecting group alteration followed by B ring formation and then stereoselective installation of the C-11 syn-hydroxy group by regioselective epoxide ring-opening using a hydride source. Ring-opening of the same epoxide intermediate with water ultimately led to the synthesis of (+)-chelamidine. The same strategy was then used to synthesize the other structurally similar B/C hexahydrobenzo[c]phenanthridine alkaloids, (+)-chelidonine, (+)-chelamidine, and (+)-norchelidonine.