A Bioinspired Synthesis of (±)‐Rubrobramide, (±)‐Flavipucine,and (±)‐Isoflavipucine

A biomimetic synthesis of naturally occurring lactams rubrobramide, flavipucine, and isoflavipucine is described. The key step is a regioselective Darzens reaction between isobutyl glyoxal and an α‐bromo‐β‐ketoamide. The construction of the core tricyclic ring system of rubrobramide was achieved by a cascade reaction in a single step from an α,β‐epoxy‐γ‐lactam. Furthermore, the absolute configuration of naturally occurring (+)‐rubrobramide was determined by vibrational circular dichroism. (±)‐Flavipucine and (±)‐isoflavipucine were synthesized from an epoxyimide, which was prepared by reaction of isobutyl glyoxal with a protected α‐bromo‐β‐ketoamide. Deprotection of the epoxyimide and formation of the pyridone ring gave (±)‐flavipucine, which was converted into (±)‐isoflavipucine by thermal isomerization.     

Biomimetic Total Synthesis of (±)‐Pallavicinolide A

Piecing it together : The first total synthesis of naturally occurring diterpene pallavicinolide A was achieved. Notable features are highlighted by three key biomimetic transformations: a base‐promoted Grob fragmentation, a singlet oxygen oxidation, and an intramolecular Diels–Alder cycloaddition.

     

Bioinspired Synthesis of (−)‐PF‐1018

The combination of electrocyclizations and cycloadditions accounts for the formation of a range of fascinating natural products. Cascades consisting of 8π electrocyclizations followed by a 6π electrocyclization and a cycloaddition are relatively common. We now report the synthesis of the tetramic acid PF‐1018 through an 8π electrocyclization, the product of which is immediately intercepted by a Diels–Alder cycloaddition. The success of this pericyclic cascade was critically dependent on the substitution pattern of the starting polyene and could be rationalized through DFT calculations. The completion of the synthesis required the instalment of a trisubstituted double bond by radical deoxygenation. An unexpected side product formed through 4‐exo‐trig radical cyclization could be recycled through an unprecedented triflation/fragmentation.     

Total Syntheses of (±)‐Fawcettimine, (±)‐Fawcettidine, (±)‐Lycoflexine,and (±)‐Lycoposerramine‐Q

The total syntheses of four fawcettimine‐related Lycopodium alkaloids, (±)‐fawcettimine, (±)‐fawcettidine, (±)‐lycoposerramine‐Q, and (±)‐lycoflexine, were completed in a highly stereoselective manner. The Pauson–Khand reaction of 4‐methylidene‐6‐siloxyoct‐1‐en‐7‐yne followed by regio‐ and stereoselective hydrogenation led to the short‐step preparation of the bicyclo[4.3.0]nonenone intermediate bearing a methyl group with the required stereochemistry. The subsequent chemical manipulation of the bicyclic compound afforded the 6‐5‐9‐membered tricyclic dioxo compound, which was then transformed into the four targeted alkaloids in an alternative and more efficient fashion.     

Total Synthesis of (±)‐Integrifolin

The total synthesis of (±)‐integrifolin has been achieved for the first time through the stereoselective preparation of the bicyclo[5.3.0]decane skeleton based on the tungsten‐catalyzed cyclization of acyclic trienynes under photoirradiation conditions. Further key transformations of the cyclized product are the Tamao oxidation through cyclic silyl ether, the introduction of two oxygen functionalities by the oxidation of the diene and the construction of three exo‐methylene moieties.     

Total Synthesis of (±)‐Strictamine

The total synthesis of strictamine has been achieved in nine steps from a known enol triflate. Characteristic features of our approach included: a) creation of a C7 all‐carbon quaternary stereocenter at an early synthetic stage; b) use of an N,N‐dimethyl tertiary amine as a surrogate of the primary amine for the rapid build‐up of a functionalized 2‐azabicyclo[3,3,1]nonan‐9‐one skeleton (achieved by using a reaction sequence of α‐bromination of the ketone, followed by a stereoconvergent intramolecular nucleophilic substitution reaction); and c) a late‐stage construction of the indolenine unit.     

Total Synthesis of (±)‐Alstoscholarisine A

The first total synthesis of the neuroactive indole alkaloid (±)‐alstoscholarisine A is reported. The key step of the concise synthesis is an efficient domino sequence that was used to assemble the 2,8‐diazabicyclo[3.3.1]nonane core through the formation of two C?N bonds and one C?C bond in a single step.     

Collective Total Syntheses of Atisane‐Type Diterpenes and Atisine‐Type Diterpenoid Alkaloids: (±)‐Spiramilactone B, (±)‐Spiraminol, (±)‐Dihydroajaconine,and (±)‐Spiramines C and D

The first total syntheses of the architecturally complex atisane‐type diterpenes and biogenetically related atisine‐type diterpenoid alkaloids (±)‐spiramilactone B, (±)‐spiraminol, (±)‐dihydroajaconine, and (±)‐spiramines C and D are reported. Highlights of the synthesis include a late‐stage biomimetic transformation of spiramilactone B, a facile formal lactone migration from the pentacyclic skeleton of spiramilactone E, a highly efficient and diastereoselective 1,7‐enyne cycloisomerization to construct the functionalized tetracyclic atisane skeleton, and a tandem retro‐Diels–Alder/intramolecular Diels–Alder sequence to achieve the tricyclo[6.2.2.0] ring system.     

Total Synthesis of (+)‐ and (±)‐Hosieine A

Described herein is a concise total synthesis of the highly potent nicotinic acetylcholine receptor ligand hosieine A in racemic and enantioenriched forms. The synthesis requires only seven steps and features a telescoped reaction sequence initiated by a gold‐catalyzed Rautenstrauch reaction.     

The Total Synthesis of (±)‐Fumimycin

The antibiotic agent fumimycin has been synthesized for the first time. This natural product was found to inhibit the bacterial peptide deformylase and may represent a lead structure to a class of novel antibacterials. Our synthetic strategy towards fumimycin involved the following steps: Dakin oxidation of an aldehyde functionality, conversion of an oxime through radical fragmentation to form an N‐diphenylphosphoryl group, construction of an α‐trisubstituted amine by 1,2‐addition to a ketimine, a Claisen rearrangement with subsequent transition‐metal‐catalyzed olefin isomerization to install a propenyl chain and final amidation.     

Total Synthesis of (±)‐Hippolachnin A

The first total synthesis of the marine polyketide (±)‐hippolachnin A has been achieved in nine linear steps and an overall yield of 9 %. Rapid access to the oxacyclobutapentalene core structure was secured by strategic application of an ene cyclization.     

A Biomimetic Synthesis of (±)‐Basiliolide B

A highly diastereoselective and practical biomimetic total synthesis of (±)‐basiliolide B has been achieved through the study of the two proposed biosynthetic pathways (O‐methylation and O‐acylation) for the unprecedented 7‐methoxy‐4,5‐dihydro‐3H‐oxepin‐2‐one (C ring). The synthesis featured a cyclopropanation/ring opening strategy for establishing the stereogenic centers at C8 and C9, a biomimetic 2‐pyrone Diels–Alder cycloaddition for the synthesis of the ABD ring system, and finally a highly efficient biomimetic intramolecular O‐acylation for the C ring formation. This result provides an important perspective on the biosynthetic origin of the unprecedented 7‐membered acyl ketene acetal moiety of the C ring.     

Total Synthesis of (±)‐Aspidophylline A

A total synthesis of aspidophylline A, a pentacyclic akuammiline‐type monoterpene indole alkaloid, is described. The synthesis features: 1) rapid access to a fully functionalized dihydrocarbazole through the desymmetrization of readily available 2‐allyl‐2‐(o‐nitrophenyl)cyclohexane‐1,3‐dione; 2) an intramolecular azidoalkoxylation of an enecarbamate to install both the furoindoline ring and the azido functionality; and 3) an intramolecular Michael addition for the construction of the 2‐azabicyclo[3.3.1]nonane ring system.     

Total Synthesis of (±)‐Phomoidride D

Described herein is a synthetic strategy for the total synthesis of (±)‐phomoidride D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by way of a tandem phenolic oxidation/intramolecular Diels–Alder cycloaddition. A subsequent SmI₂‐mediated cyclization cascade delivers an isotwistane intermediate poised for a Wharton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion.     

Synthesis of (±)‐Lasubine II Using N‐Methoxyamines

The synthesis of (±)‐lasubine II has been achieved through a three‐component allylation capitalizing on the unique properties of N‐methoxyamines. This reaction enabled the installation of all the carbon atoms of lasubine II in a single operation. The N‐methoxy group was efficiently used for the subsequent nitrone formation. A single‐step cyclization of isoxazolidines or N‐methoxyamines to form functionalized piperidine rings was also developed.