Short diastereoselective synthesis of the C1-C13 (AB spiroacetal) and C17-C28 fragments (CD spiroacetal) of spongistatin 1 and 2 through double chain-elongation reactions

A unique and practical synthetic sequence for rapid access to polyketides and to further the spiroacetals derived from them, which utilizes a bidirectional Hosomi-Sakurai allylation approach around key allylsilanes in the synthesis of the AB and CD ring systems of spongistatin 1 and 2, is reported. The synthesis of the AB spiroacetal 9 requires 13 steps, with a longest linear sequence of seven steps in an overall yield of 27%. The synthesis of the CD spiroacetal 13 requires 15 steps, with a longest linear sequence of 11 steps in an overall yield of 30%. Both syntheses start from but-3-enol.     

Total synthesis of cis-solamin: exploiting the RuO4-catalyzed oxidative cyclization of dienes

[structure: see text] An enantioselective total synthesis of cis-solamin has been accomplished using a highly diastereoselective ruthenium tetroxide catalyzed oxidative cyclization as a crucial transformation. Further key steps involved an enzymatic desymmetrization, a TPAP-catalyzed oxidative termini differentiation, and a ruthenium-catalyzed Alder-ene reaction. Thus, the total synthesis of cis-solamin was achieved in 11 steps with an overall yield of 7.5%.     

An aldol approach to the synthesis of the anti-tubercular agent erogorgiaene

A total synthesis of erogorgiaene is described in 16 steps. The synthesis relies upon a highly diastereoselective intramolecular Friedel-Crafts reaction of an oxetane derived via an asymmetric syn aldol coupling.     

A Chiron-based Approach for the Synthesis of Tricyclic Tyrosine Analogue

A chiron approach-based enantioselective synthesis of designed tricyclic tyrosine analogue D-2 was developed. A SmI2-mediated free radical cyclization, an intramolecular Friedel-Crafts reaction and an intramolecular Mannich reaction served as key steps. These key steps were optimized and repeated in good yields. All the stereochemistries in the synthesis were established and confirmed.     

Synthesis of the C(2)-C(13) fragment (the A-B spiroketal unit) of spongistatin 1 (altohyrtin A): use of a common intermediate for the synthesis of both spongistatin spiroketals

[reaction: see text] A convergent synthesis of 14 corresponding to the A-B spiroketal core of spongistatin 1 has been accomplished via an iodo-spiroketalization reaction of glycal 9, which was synthesized in three steps from a late-stage intermediate used in our synthesis of the C-D spiroketal fragment of spongistatin 1. Elaboration of 14 to the A-B spiroketal 15 was accomplished in three steps.     

Furanosteroid studies. Improved synthesis of the A,B,C,E-ring core of viridin

The tetracyclic core skeleton of the furanosteroid viridin is prepared in nine steps from readily available materials. The key step in the synthesis is a facile acid-promoted cyclodehydration of an aryloxyketone to prepare the benzofuran moiety. From this intermediate, the known target skeleton is prepared in four steps. This new synthesis is a six-step improvement over the previously reported one.     

A Unified Approach for the Assembly of Atisine‐ and Hetidine‐type Diterpenoid Alkaloids: Total Syntheses of Azitine and the Proposed Structure of Navirine C

A tetracyclic dinitrile was synthesized in twelve steps from cyclohex‐2‐en‐1‐one by using a chelation‐triggered conjugate addition to a γ‐hydroxy‐substituted α,β‐unsaturated nitrile and an oxidative dearomatization/Diels–Alder cycloaddition cascade as the key steps. The first total synthesis of azitine (in 17 steps) was achieved through a simple reductive cyclization of this intermediate and subsequent transformations while the total synthesis of the proposed structure of navirine C (in 19 steps) was accomplished by a hydrogen‐atom‐transfer reaction of the tetracyclic dinitrile, Pd/C‐catalyzed reductive cyclization, and subsequent functional group manipulation.     

A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B

Recent reports of antiepileptic activity of the fungal alkaloid TMC-120B have renewed the interest in this natural product. Previous total syntheses of TMC-120B comprise many steps and have low overall yields (11–17 steps, 1.5–2.9% yield). Thus, to access this compound more efficiently, we herein present a concise and significantly improved total synthesis of the natural product. Our short synthesis relies on two key cyclization steps to assemble the central scaffold: isoquinoline formation via an ethynyl-imino cyclization and an intramolecular Friedel-Crafts reaction to form the furanone.     

Enantioselective allyltitanations and metathesis reactions. Application to the synthesis of piperidine alkaloids (+)-sedamine and (-)-prosophylline

An enantioselective synthesis of the piperidine alkaloids (+)-sedamine and (-)-prosophylline is reported. The synthesis of (+)-sedamine has been achieved in 12 steps with an overall yield of 20% from benzaldehyde, and (-)-prosophylline was obtained in 15 steps with an overall yield of 9.2%, starting from D-glyceraldehyde acetonide 14. The key steps are enantioselective allyltitanation reactions and ring-closing or cross-metathesis reactions.     

Stereoselective synthesis of the macrolactone core of (+)-neopeltolide

A stereoselective synthesis of the macrolactone core of the potent anticancer agent neopeltolide is disclosed. The key steps of the synthesis include asymmetric allylation using Krische' protocol, conjugate reduction using MacMillan's methodology, and an asymmetric hetero-Diels-Alder reaction using Jacobsen's catalyst. Substrate controlled diastereoselective 1,3-anti reduction of a keto alcohol, Luche reduction followed by Ireland-Claisen rearrangement, oxymercuration, and reductive lithiation are other key steps.     

Stereoselective synthesis of 2,6-disubstituted 3-piperidinols: application to the expedient synthesis of (+)-julifloridine

[reaction: see text] The asymmetric synthesis of 2,6-disubstituted 3-piperidinols having a 2,3-cis and 2,6-trans relative stereochemistry was accomplished in three steps using the following sequence: stereocontrolled nucleophilic addition of an organomagnesium reagent to a chiral pyridinium salt; monohydrogenation of the resulting 2-substituted 1,2-dihydropyridine; and a one-pot, highly diastereoselective epoxidation-nucleophilic addition with a heteroatom nucleophile or an organometallic reagent. This methodology was applied to the expedient asymmetric synthesis of (+)-julifloridine in four steps.     

The first total synthesis of the natural product angoluvarin

The total synthesis of angoluvarin, a member of the dihydrochalcone family of natural products, is reported. Starting with 2-bromophenol, the synthesis was accomplished in eight steps with an overall yield of 2%. This represents the first reported synthesis of angoluvarin.     

Utility of the ammonia-free Birch reduction of electron-deficient pyrroles: total synthesis of the 20s proteasome inhibitor, clasto-lactacystin beta-lactone

A new synthesis of the 20S proteasome inhibitor clasto-lactacystin beta-lactone is described. Our route to this important natural product involves the partial reduction of an electron deficient pyrrole as a key step. By judicious choice of enolate counterion, we were able to exert complete control over the stereoselectivity of the reduction/aldol reaction. Early attempts to complete the synthesis by using a C-4 methyl substituted pyrrole are described in full, together with our attempts to promote regioselective elimination of a tertiary alcohol. The lessons learnt from this first approach led us to develop another, and ultimately successful, route that introduced the C-4 methyl group at a late stage in the synthesis. Our successful route is then described and this contains several highly stereoselective steps including a cis-dihydroxylation and an enolate methylation. The final synthesis proceeds in just 13 steps and in 15 % overall yield making it an extremely efficient route to this valuable compound.     

Enantioselective Total Synthesis of the Lignan (+)‐Linoxepin

An enantioselective total synthesis of the natural (+)‐linoxepin ( 1 ) was accomplished in eleven steps from bromovanin ( 24 ). Key steps are a domino carbopalladation/ Mizoroki–Heck reaction with the formation of a pentacyclic system, an asymmetric hydroboration as well as an oxidative lactonization.     

Towards the synthesis of Palmerolide A: asymmetric synthesis of C1–C14 fragment

The synthesis of a C1–C14 fragment of a marine cytotoxic natural product Palmerolide A is described. The key steps involved in this synthesis are deoxygenative rearrangement of an alkynol followed by an asymmetric dihydroxylation of a diene ester and CBS-reduction.     

A convergent approach for the total synthesis of the α-glucosidase inhibitor (−)-panaxjapyne-C

The stereoselective total synthesis of (?)-panaxjapyne-C was accomplished in a convergent fashion. The synthesis utilizes the readily available enantiomers l-(+)-diethyltartrate and d-(?)-diethyltartrate and involves a Cadiot–Chodkiewicz coupling reaction, and an Ohira–Bestmann reaction as the key steps.     

Synthetic Studies on the Ambiguine Family of Alkaloids: Construction of the ABCD Ring System

A racemic synthesis of the ABCD ring core of the ambiguines that preserves the tertiary alcohol has been accomplished in a convergent synthesis in 10 synthetic steps, in an overall yield of 46% from commercially available 4-bromoindole and m-methylanisole.     

A concise and improved synthesis of (+)-eleutherin, (+)-allo-eleutherin and a formal synthesis of (+)-nocardione B

A concise and improved stereoselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and the formal synthesis of (+)-nocardione B is described. The synthesis is based on a Dötz benzannulation and an improved oxa-Pictet-Spengler cyclization as the key steps. The synthesis is achieved in six steps in overall yields of 18% for eleutherin and 20% for allo-eleutherin.     

Expedient total synthesis of pyrrothine natural products and analogs

This paper describes an expedient and straightforward total synthesis of the two pyrrothine natural products holomycin (7 steps, 11% overall) and xenorhabdin I (7 steps, 11% overall) and analogs thereof via a common late-stage intermediate. The pathway proceeds via the pyrrothine hydrochloride intermediate (6 steps, 17% overall) which also gave access to very fast synthesis of analogs as demonstrated by the synthesis of , and (7 steps, 11-12% overall).     

Approach to the synthesis of cladiell-11-ene-3,6,7-triol

[reaction: see text] The synthesis of an advanced intermediate in the synthesis of the title compound has been achieved. Key steps include an Ireland-Claisen rearrangement to install the C7 tertiary alcohol stereocenter, an SN2' reaction of an alkoxymethyl Cu reagent, and a diastereoselective Re-catalyzed allylic alcohol transposition.