A new ring expansion for a chiral hexahydroazulene skeleton possessing an angular methyl group

A new synthetic route for a pseudoguaiane ring system is described. The synthesis features an Ireland-Claisen rearrangement for constructing the trans-fused ring system, followed by a new ring expansion to yield a bicyclo[5.3.0]decane ring system possessing an angular methyl group.     

Asymmetric Total Synthesis of Propindilactone G,Part 2: Enantioselective Construction of the Fully Functionalized BCDE Ring System

The enantioselective synthesis of the fully functionalized BCDE tetracyclic ring system of propindilactone G ( A ) is reported. Several synthetic methods were developed and applied to achieve this goal, including: 1) an asymmetric Diels–Alder reaction in the presence of Hayashi′s catalyst for the synthesis of optically pure key intermediate 3 ; 2) an intramolecular Pauson–Khand reaction (PKR) for the stereoselective synthesis of the BCDE ring with an all‐carbon chiral quaternary center at the C13 position by using the TMS‐substituted acetylene as the substrate; and 3) Pd‐catalyzed reductive hydrogenolysis for the stereoselective synthesis of the fully functionalized BCDE tetracyclic ring system. The chemistry developed herein provided a greater understanding of the total synthesis propindilactone G ( A ) and its analogues.     

Total synthesis of (+/-)-scopadulin.

The first total synthesis of (+/-)-scopadulin, an aphidicolane diterpene, is described. The core structure (A/B/C/D ring system) was constructed by an initial synthesis of the B/C/D ring system by our reported methods and a subsequent A ring cyclization by intramolecular aldol condensation. A highly stereoselective cyanation of the tetracyclic enone by Et2AlCN gave a trans-fused A/B ring system with a beta-cyanide at C-4. Stereoselective construction of a quaternary carbon at C-4 was achieved by alpha-alkylation of the cyano group and conversion of the sterically hindered cyano group to a methyl group via our novel reaction for conversion of primary aliphatic amines into alcohols. Finally, the total synthesis of (+/-)-scopadulin was accomplished by a highly chemo- and stereoselective methylation at C-16 and modification of the C-4 alpha-functionality. The stereoselectivity observed in the MeTi(O-i-Pr)3-mediated methylation for the generation of a tertiary axial alcohol at C-16 is extremely high.     

A simple approach for the synthesis of azocine alkaloids: The total synthesis of megallanesine

A new three step synthetic route to construct azocine ring system using anion chemistry and intramolecular Friedel-Craft reaction of an ester is presented. This method allows synthesis of azocine ring analogues in excellent overall yields. The designed strategy was applied for the synthesis of naturally occurring magallanesine.     

Synthesis of the ABCD fragment of gymnocin-B

A convergent synthesis of the ABCD fragment of gymnocin-B was accomplished. The tetracyclic ether ring system was synthesized by the construction of the BC ring system via the oxiranyl anion alkylation and ring expansion reaction, followed by the formation of the five-membered A-ring via a stereoselective radical cyclization reaction of a neopentyl-type iodide.     

A facile synthesis of an unsymmetric benzopyranobenzopyran ring system

A facile route to the synthesis of an unsymmetric benzopyranobenzopyran ring system is described. A key feature of this synthesis incorporates a tandem deprotection-cyclization strategy to construct the C-ring of the tetracyclic system.     

Synthetic studies towards the phomactins. Concise syntheses of the tricyclic furanochroman and the oxygenated bicyclo[9.3.1]pentadecane ring systems in phomactin A

A concise synthesis of the tricyclic furanochroman unit 3 found in the PAF antagonist phomactin A (1) isolated from the marine fungus Phoma sp., is described. In complementary studies, a variety of synthetic routes towards the bicyclo[9.3.1]pentadecane ring system 4 in phomactin A were explored. These studies culminated in a synthesis of the substituted ring system 79 containing all the carbon atoms and all the necessary oxygen centres for elaboration to phomactin A itself.     

Total synthesis of bryostatins: the development of methodology for the atom-economic and stereoselective synthesis of the ring C subunit

Bryostatins, a family of structurally complicated macrolides, exhibit an exceptional range of biological activities. The limited availability and structural complexity of these molecules makes development of an efficient total synthesis particularly important. This article describes our initial efforts towards the total synthesis of bryostatins, in which chemoselective and atom-economical methods for the stereoselective assembly of the ring C subunit were developed. A Pd-catalyzed tandem alkyne-alkyne coupling/6-endo-dig cyclization sequence was explored and successfully pursued in the synthesis of a dihydropyran ring system. Elaboration of this methodology ultimately led to a concise synthesis of the ring C subunit of bryostatins.     

A novel synthesis of the carbapen-2-em ring system

A new synthesis of the carbapenem ring system, as found in thienamycin and related natural products, has been developed. The key step involves a highly efficient carbene insertion reaction which produces the bicyclic ring system by forming the N3 bond.     

A strategy for the synthesis of the fargenone/fargenin family of natural products: synthesis of the tricyclic core

A synthesis of the core ring structure of the fargenin/fargenone family of natural products is presented. The general strategy is based upon biosynthetic speculation and exploits a cascade reaction, which transforms a spirocyclic dienone into the core ring system via a deprotonation-oxy-Michael-Wittig olefination sequence. This study represents the first synthesis work towards this family of natural products.     

Total Synthesis of (−)-Glaucocalyxin A

A practically useful method for the formation of the highly oxygenated bicyclo[3.2.1]octane ring system through Mn(OAc)₃-mediated radical cyclization of alkynyl ketones was developed, which opens up a new avenue for the total synthesis of a number of highly oxidized diterpenoids. Application of this method enabled the first total synthesis of (−)-glaucocalyxin A. Other salient features of the synthesis include a highly enantioselective conjugate addition/acylation cascade reaction, a Yamamoto aldol reaction, and an intramolecular Diels–Alder reaction to assemble the A/B ring system.     

Synthesis of ACE tricyclic systems of daphnicyclidin A and dehy-droxymacropodumine A

The synthesis of the ACE tricyclic system of daphnicyclidin A and dehydroxymacropodumine A are developed. The key reactions include an efficient aldol reaction to introduce chiral fragment 33 for further construction of piperidine ring B and seven-membered ring C, a nucleophilic addition of lithium pentene to aldehyde for installation of ring E, and a photocatalytic decarboxylation conjugate addition to construct ring C.     

Synthesis of taxane ABC tricyclic skeleton from lycoctonine

A new conversional synthesis of the ABC ring system of taxoids from the C19-diterpenoid alkaloid lycoctonine was developed in 6 steps with 2% overall yield. The distinctive features of the conversion include pinacol rearrangement, enlargement of ring B, and opening of a four-membered ring.     

Synthesis and Diels-Alder reactions of the benzo[4,5]thieno [2,3-c]pyrrole ring system

The first synthesis of the parent compound of the benzo[4,5]thieno[2,3-c]pyrrole ring system and its derivatives, as well as their Diels-Alder reactions with DMAD and N-phenylmaleimide are reported. A new synthesis of the benzo[4,5]thieno[2,3-d]pyridazine ring system is also described.     

Iterative synthesis of the ABCDEF-ring system of yessotoxin and adriatoxin

A stereocontrolled linear synthesis of the ABCDEF-ring system of yessotoxin and adriatoxin, diarrhetic shellfish toxins, is described. Iterative application of a tetrahydropyran synthesis by reaction of the alkylation of a sulfonyl-stabilized oxiranyl anion followed by 6-endo cyclization of a 4,5-epoxy alcohol led to the synthesis of the trans-fused hexacyclic ether system, and the seven-membered E ring was constructed by ring expansion reaction.     

The synthesis of 4H-imidazo[5,1-c][1,4]benzothiazine derivatives

A facile synthesis of the 4H-imidazo[5,1-c][1,4]benzothiazine ring system is described. The synthesis utilized the annulation of an imidazole ring onto a 2H-1,4-benzothiazin-3(4H)-one via the addition of the anion of ethyl isocyanoacetate. Methods for the functionalization of the 1-, 3-, 4-, and 5-positions of the ring system are presented.     

Highly stereoselective construction of 4,6-cis-substituted quinolizidine ring core: an application to enantioselective total synthesis of the marine alkaloid clavepictines A, B and pictamine

The enantioselective total synthesis of the marine alkaloids clavepictines A, B and pictamine has been achieved through the highly stereocontrolled quinolizidine ring closure of the conformationally constrained piperidine ring system (2), which bears the chiral centers and appropriate functionality needed for the synthesis of target alkaloids. The absolute stereochemistry of clavepictines and pictamine was verified to be 3R, 4S, 6S, 9aS by the present synthesis.     

Total Synthesis of (−)‐Glaucocalyxin A

A practically useful method for the formation of the highly oxygenated bicyclo[3.2.1]octane ring system through Mn(OAc)₃‐mediated radical cyclization of alkynyl ketones was developed, which opens up a new avenue for the total synthesis of a number of highly oxidized diterpenoids. Application of this method enabled the first total synthesis of (?)‐glaucocalyxin A. Other salient features of the synthesis include a highly enantioselective conjugate addition/acylation cascade reaction, a Yamamoto aldol reaction, and an intramolecular Diels–Alder reaction to assemble the A/B ring system.     

Synthesis of bruguierol A employing ring closing metathesis

An expedient synthesis of bruguierol A encompassing a novel 2,3-benzo-8-oxabicyclo[3.2.1]octane ring system is described employing ring closing metathesis to generate the oxa-bridged tricyclic core.     

Convergent synthesis of the FGHI ring system of yessotoxin: stereoselective construction of the G ring

A convergent synthetic route to the FGHI ring system of yessotoxin, a marine ladder polyether, has been developed. The synthesis features convergent coupling of the diol and the aldehyde to form α-cyano ethers via acetal formation followed by ring closing metathesis and reductive etherification to construct the oxocane ring G and tetrahydropyran ring H, respectively. The β-methyl group on the G ring was stereoselectively introduced by alkylation of the corresponding ketone.