Total Synthesis of (−)‐Cleistenolide

An efficient and short total synthesis of (?)‐cleistenolide ( 1 ) from D ‐mannitol with an overall yield of 23.6% is described. The chiron approach for the synthesis of (?)‐cleistenolide involves a one‐C‐atom Wittig olefination, a selective allylic triethylsilyl protection, and a Grubbs‐catalyzed ring‐closure‐metathesis (RCM) reaction as the key steps.     

Asymmetric Total Synthesis of (−)‐Cladospolide B

An enantioselective total synthesis of (?)‐cladospolide B was described. The key steps in this synthesis include(a) a Sharpless asymmetric dihydroxylation to elaborate syn diol at C‐4 and C‐5 positions; (b) a Mitsunobu esterification to reverse the configuration at C‐11 from (S) to (R); and (c) a ring‐closing metathesis to access the 12‐membered macrocyclic ring.     

Ring‐Closing Metathesis and Photo‐Fries Reaction for the Construction of the Ansamycin Antibiotic Kendomycin: Development of a Protecting Group Free Oxidative Endgame

Two convergent total syntheses of the ansa‐polyketide (?)‐kendomycin ( 1 ) are described. The syntheses benefit from the use of readily available and cheap starting materials. Highly complex diastereoselective Claisen–Ireland rearrangements were used to introduce the (E)‐double bond and the C16‐Me group. The ring closure of the strained ansa macrocycle was achieved by ring‐closing metathesis and a highly efficient combination of macrolactonization and photo‐Fries reaction. A protecting group free endgame via an unstable o‐quinone is presented. Additionally some unsuccessful synthetic efforts towards the total synthesis of 1 are described.     

Formal Total Synthesis of (−)‐Apicularen A by a Strategy Based on Ring‐Closing Metathesis and Transannular Cyclization

A formal synthesis of (?)‐apicularen A, a potent antitumor agent with unique biological properties, has been completed in a 15‐step sequence starting from a known, enantiomerically pure hydroxyepoxide, which was generated by using the Jacobsen hydrolytic‐kinetic‐resolution methodology. The 12‐membered macrocyclic lactone in the target was constructed by ring‐closing metathesis, and the trans‐tetrahydropyran ring system was created through the transannular etherification of a hydroxyalkene.     

Synthetic Studies Toward (+)‐Spongidepsin

A convergent enantiomerically controlled synthetic effort toward (+)‐spongidepsin is reported. The synthesis benefits from the use of readily available and inexpensive starting materials like D ‐mannitol and (?)‐β‐citronellene. Key transformations include Evans asymmetric methylation, Mitsunobu esterification, (1H‐benzotriazol‐1‐yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP)‐mediated amide formation for the preparation of a fully functionalized acyclic precursor, and ring‐closing metathesis (RCM).     

Total Synthesis of (−)‐Lundurine A and Determination of its Absolute Configuration

A 15‐step total synthesis of (?)‐lundurine A ( 1 ) from easily accessible (S)‐pyrrolidinone 18 is reported. A Simmons‐Smith reaction allows the efficient, simultaneous assembly of the cyclopropyl C ring, the six‐membered D ring, the seven‐membered E ring, and the quaternary carbon stereocenters at C2 and C7. The absolute configuration of natural (?)‐lundurine A was deduced to be 2R,7R,20R based on the stepwise construction of the stereocenters during the total synthesis.     

Formal Synthesis of (−)‐Cyclaradine Using Ring Closing Metathesis

The stereoselective formal synthesis of (?)‐cyclaradine from the inexpensively available starting material L ‐glutamic acid is described, using Eschenmoser's reagent, and applying Luche reduction, Grignard reaction, and ring closing metathesis (RCM) as the key steps.     

Stereoselective total synthesis of (-)-spirofungin A by utilising hydrogen-bond controlled spiroketalisation

The stereoselective total synthesis of the spiroketal containing Streptomyces metabolite (?)‐spirofungin A ( 1 ) is described. A key step involved a spiroketalisation controlled by an intramolecular H‐bond which favoured the desired spiroketal 4 (13:1 ratio). The presence of the intramolecular H‐bond in 4 is possibly due to a 1,5‐alkyne–oxygen interaction. Other key steps include an efficient cross‐metathesis to form the spiroketal precursor, a tin mediated syn‐aldol reaction and a Stille cross‐coupling reaction to create the C22? C23 bond. A final Wittig extension followed by deprotection gave (?)‐spirofungin A ( 1 ).     

Stereoselective Synthesis of (−)‐Pinidinone

A simple and efficient stereoselective linear approach to the total synthesis of (?)‐pinidinone has been accomplished starting from propane‐1,3‐diol, and employing Maruoka asymmetric allylation and Grubbs' olefin cross‐metathesis as the key steps.     

Asymmetric Total Synthesis of Stagonolide G

A simple asymmetric total synthesis of stagonolide G ( 1 ) is described. Asymmetric dihydroxylation, regioselective epoxide ring opening, and vinyl Grignard reactions are involved in generating the stereogenic centers C(4) and C(8), followed by Grubbs‐II‐catalyzed ring‐closing metathesis (RCM).     

Indole‐Diterpene Synthetic Studies: Total Synthesis of (−)‐21‐Isopentenylpaxilline

An efficient, stereocontrolled total synthesis of the complex indole‐diterpene alkaloid (?)‐21‐isopentenylpaxilline ( 1 ) has been achieved. Key elements of the synthesis include the stereocontrolled construction of the advanced eastern hemisphere (?)‐ 68 , involving a highly efficient union of the eastern and western fragments (?)‐ 68 and 5 exploiting our 2‐substituted indole synthesis, application of the Negishi π cycloalkylation tactic as a new, potentially general protocol for the construction of ring C, and the fragmentation of a β,γ‐epoxy ketone to introduce the tertiary OH group at C(13) in the indole diterpene skeleton.     

群柱虫内酯官能团化的C2-C10片段的立体选择性合成

本文以廉价的消旋甲基戊二酸酐为起始原料,完成了具有抗肿瘤活性的海洋天然产物群柱虫内酯（Clavulactone）官能团化的C2-C10片段的立体选择性合成。使用的关键方法包括不对称去对称化获得光学纯手性孤立甲基,和RCM方法构建顺式烯烃。该片段的获得为群柱虫内酯的全合成提供了基础。     

Enantioselective Synthesis of (−)‐(R)‐Cordiachromene and (−)‐(R)‐Dictyochromenol Utilizing Intramolecular SNAr Reaction

A simple and efficient enantioselective synthesis of chromene, (?)‐(R)‐cordiachromene ( 1 ), and (?)‐(R)‐dictyochromenol ( 2 ) has been accomplished. This convergent synthesis utilizes intramolecular S_NAr reaction for the formation of chroman ring, and Seebach's method of ‘self‐reproduction of chirality’ should establish the (R)‐configuration of the C(2) side chain as key steps.     

Stereoselective Total Synthesis of Stagonolide C

A convergent and efficient total synthesis of stagonolide C ( 1 ), a phytotoxic metabolite, was achieved (Schemes 2 and 3) The synthesis exploited the high configuration control in the Prins cyclization along with alkene rearrangement and ring‐closing metathesis as key steps.     

Formal synthesis of (−)-stemoamide using a useful epimerization at C-8

The formal synthesis of (?)-stemoamide was achieved starting from l-pyroglutamic acid. The key steps used are the allylation using BF₃·OEt₂, ring closing metathesis, allylic oxidation and a novel epimerization at C8.     

Asymmetric Total Synthesis of (−)‐Stenine and 9a‐epi‐Stenine

A route for the asymmetric synthesis of (?)‐stenine, a member of the Stemona alkaloid family used as folk medicine in Asian countries, is described. The key features of the sequence employed include stereoselective transformations on a cyclohexane ring controlled by a chiral auxiliary unit and an intramolecular Mitsunobu reaction to construct the perhydroindole ring system. By using an intermediate in the route to (?)‐stenine, an asymmetric synthesis of 9a‐epi‐stenine was also executed. The C(9a) stereocenter in 9a‐epi‐stenine was installed by using a Staudinger/aza‐Wittig reaction of a keto–azide precursor followed by reduction of the resulting imine. The results of this effort demonstrate the applicability of the chiral auxiliary based strategy to the preparation of naturally occurring alkaloids that contain highly functionalized cyclohexane cores.     

Total Synthesis of (−)‐Nakadomarin A

A highly efficient 12‐step synthesis of the marine alkaloid (?)‐nakadomarin A has been accomplished. The key advanced intermediate, a tetracyclic ketone derivative, was constructed in just seven steps using a sequence that includes an asymmetric Pauson–Khand reaction, an Overman rearrangement reaction, a ring‐closing metathesis reaction, and an amination reaction. Late introduction of the furan ring during the synthesis of (?)‐nakadomarin A means that the key tetracyclic ketone derivative has the potential to serve as an advanced intermediate for the synthesis of related marine alkaloids.     

Organocatalytic,Asymmetric Total Synthesis of (−)‐Haliclonin A

The first total synthesis of the alkaloid (?)‐haliclonin A is reported. The asymmetric synthesis relied on a novel organocatalytic asymmetric conjugate addition of nitromethane with 3‐alkenyl cyclohex‐2‐enone to set the stereochemistry of the all‐carbon quaternary stereogenic center. The synthesis also features a Pd‐promoted cyclization to form the 3‐azabicyclo[3,3,1]nonane core, a SmI₂‐mediated intermolecular reductive coupling of enone with aldehyde to form the requisite secondary chiral alcohol, ring‐closing alkene and alkyne metathesis reactions to build the two aza‐macrocyclic ring systems, and an unprecedented direct transformation of enol into enone.     

Cyclic 1,2‐Diketones as Core Building Blocks: A Strategy for the Total Synthesis of (−)‐Terpestacin

We report a full account of our work towards the total synthesis of (?)‐terpestacin ( 1 ), a sesterterpene originally isolated from fungal strain Arthrinium sp. FA1744. Its promising anti‐HIV and anti‐cancer activity, as well as its novel structure, make terpestacin an attractive synthetic target. A strategy based on the unique reactivity of cyclic 1,2‐diketones (diosphenols) was developed and total synthesis of 1 was achieved in 20 steps, in the longest linear sequence, from commercially available 2‐hydroxy‐3‐methyl‐2‐cyclopenten‐1‐one. The key feature of our synthesis is the double usage of a “Pd AAA‐Claisen” protocol (AAA=asymmetric allylic alkylation), first in the early stages to generate the C1 quaternary center and then in the late stages to install the side chain. In addition, a rather unusual ene‐1,2‐dione moiety was synthesized and utilized as an excellent Michael acceptor to attach the C15 substituent. Several possible routes towards the total synthesis have been examined and carefully evaluated. During our exploration many interesting chemoselectivity issues have been addressed, such as a highly selective ring‐closing metathesis and a challenging oxidation of a disubstituted olefin in the presence of three trisubstiuted ones.     

Total Synthesis of Marine Eicosanoid (−)‐Hybridalactone

(?)‐Hybridalactone ( 1 ) is a marine eicosanoid isolated from the red alga Laurencia hybrida. This natural product contains cyclopropane, cyclopentane, 13‐membered macrolactone and epoxide ring systems incorporating seven stereogenic centers. Moreover, this compound has an acid‐labile skipped Z,Z‐diene motif. In this paper, we report on the total synthesis of (?)‐hybridalactone ( 1 ). The unique eicosanoid (?)‐hybridalactone ( 1 ) was synthesized starting from optically active γ‐butyrolactone 2 in a linear sequence comprising 21 steps with an overall yield of 21.9 %. A key step in the synthesis of (?)‐hybridalactone ( 1 ) is the methyl phenylsulfonylacetate‐mediated one‐pot synthesis of the cis‐cyclopropane‐γ‐lactone derivative. This reaction provided an efficient and stereoselective access to cis‐cyclopropane‐γ‐lactone 12 . Further elaboration of the latter compounds through desulfonylation, epoxidation, oxidation, Wittig olefination and Shiina macrolactonization afforded (?)‐hybridalactone.