A cross metathesis strategy for the synthesis of highly functionalized conjugated cyanodienes: synthesis of the C3-C17 framework of (−)-borrelidin

A cross metathesis strategy for the synthesis of highly functionalized conjugated cyanodienes was developed and was successfully applied in the synthesis of the C3-C17 framework of (−)-borrelidin.     

Formal total synthesis of borrelidin: synthesis of C1-C11 fragment via desymmetrization strategy

A stereoselective formal total synthesis of borrelidin is described. The synthetic strategy for synthesis of C1-C11 fragment features desymmetrization of Diels-Alder adduct, Sharpless asymmetric epoxidation, regioselective opening of chiral epoxide, and alkylation using Evans chiral auxiliary.     

First enantioselective total synthesis of (−)-heliannuol C

The first, efficient total synthesis of (−)-heliannuol C (1) was accomplished enantioselectively, using a chemoenzymatic desymmetrization of the σ-symmetrical diol, a ring closing metathesis, a diastereoselective epoxidation, and a regioselective reductive cleavage of epoxide as the key reaction steps.     

Facile synthesis of (−)-6-acetoxy-5-hexadecanolide by size-selective ring-closing/cross metathesis

A total synthesis of (−)-6-acetoxy-5-hexadecanolide, in six steps and 37% overall yield from (2R,3S)-1,2-epoxy-4-penten-3-ol is reported. The key synthetic step is a size-selective ring-closing/cross metathesis reaction in which lactone formation and alkyl chain extension are accomplished in an efficient one-pot process.     

Studies towards the total synthesis of narbonolide: stereoselective preparation of the C1-C10 fragment

An efficient stereoselective synthesis of the C1-C10 fragment of narbonolide is reported. The stereocentres at C2, 3, 4, 5, 8 and 9 in fragment 5 can be generated via an iterative asymmetric acyl-thiazolidinethione aldol reaction, whereas the stereocentre at C6 is installed by means of Myers alkylation.     

Stereoconvergent synthesis of the C1-C11 and C12-C24 fragments of (−)-macrolactin-A

Stereoconvergent syntheses of the C1-C11 and C12-C24 fragments of (−)-macrolactin-A are reported.     

Studies towards the total synthesis of (−)-callystatin A

The synthesis of C₁-C₁₂ and C₁₃-C₂₂ fragments of (−)-callystatin A is accomplished employing desymmetrization strategy for the creation of five chiral centres of the polypropionate fragment and application of cross-metathesis (CM) reaction for the first time for this molecule.     

Stereoselective synthesis of (−)-gabosine C using a Nozaki-Hiyama-Kishi reaction and RCM

An efficient synthesis of (−)-gabosine C 3 and a formal synthesis of (−)-COTC 4 are described using the Nozaki-Hiyama-Kishi (NHK) reaction and RCM as the key steps.     

Studies on the total synthesis of sanglifehrin A: stereoselective synthesis of the C(29)-C(39) fragment

A highly stereoselective synthesis of the C(29)-C(39) fragment of the potent immunosuppressant sanglifehrin A has been accomplished by a sequence involving 16 steps (18% overall yield) from N-propionyloxazolidinone 9. Key steps are a diastereoselective hydroboration, and a diastereoselective epoxidation of an allylic alcohol followed by a 1,5-anti boron-mediated aldol reaction of methyl ketone 4 with chiral aldehyde 5.     

Studies towards the total synthesis of Phostriecin

A synthetic approach toward the phostriecin, an antitumor natural product is described. The key features of the present synthesis are Wittig reaction, synthesis of homoallylic alcohol using Brown’s protocol (alkoxyallylboration) and RCM for the creation of unsaturated lactone moiety of phostriecin.     

Studies towards the total synthesis of cruentaren A and B: Stereoselective synthesis of fragments C1-C11, C12-C22 and C23-C28

A convergent and stereoselective approach for the synthesis of C1-C11, C12-C22, and C23-C28 fragments of cytotoxic natural products cruentaren A and B are accomplished. Highlights of the strategy include a Sharpless epoxidation followed by a regioselective opening of epoxide to generate anti and syn-stereochemistry at C9-C10 and C15-C16, an Alder-Rickert reaction between a 1,5-dimethoxy-1,4-cyclohexadiene and dienophile to construct the aromatic ring, and a lithium-mediated aldol reaction to install the C17-C18 anti-stereochemistry. The synthesis of C1-C11 and C12-C22 fragments proceed with a longest linear sequence of 10 and 17 steps from commercially available 2-butyne-1,4-diol and cis-2-butene-1,4-diol respectively.     

Concise enantioselective synthesis of (−)-lasubine II

An enantioselective synthesis of the quinolizidine alkaloid (−)-lasubine II 1 is reported. Two different pathways to the key intermediate 2 are described. The first case involving a sequence of ring rearrangement metathesis (RRM), simple functional group interconversion operations, followed by a stereoselective cross metathesis (CM) and in the second case a domino ring opening-/ring closing-/cross metathesis step is involved. In both cases, following the metathesis reactions, exclusively the E-isomer was obtained. The final cyclisation towards the quinolizidine skeleton is achieved by an intramolecular Michael reaction. This concept represents the first example of a highly stereoselective RRM-CM combination in the synthesis of a natural product.     

An efficient total synthesis of (−)-anamarine

An efficient synthesis of (−)-anamarine is described using d(+)-mannitol and (R)-epichlorohydrin. The synthesis is achieved starting from easily accessible d(+)-mannitol using a selective benzoylation, regioselective epoxide ring opening, a selective acetonide deprotection, tosylation and cross metathesis reaction.     

Stereoselective synthesis of the C(1)-C(11) fragment of peloruside A

A highly stereoselective synthesis of the C(1)-C(11) fragment 4 of peloruside A has been accomplished via a stereoselective double allylboration and an intramolecular epoxide opening to provide the functionally dense C(3)-C(11) segment 14. A glycolate aldol reaction was then employed to introduce the remaining stereocenters at C(2)-C(3). [reaction: see text]     

A cross metathesis approach to the synthesis of the C11-C23 fragment of (−)-16-normethyldictyostatin

The synthesis of the C11-C23 fragment 2 of (−)-16-normethyldictyostatin has been achieved by cross metathesis between two olefinic fragments 4 and 5 followed by a reduction of the double bond at C16-C17. Both the olefinic fragments are easily synthesized in a diastereoselective manner from the common precursor alcohol 7.     

Synthesis of the C7-C24 fragment of (−)-Macrolactin F

An enantioselective and convergent synthesis of the C7-C24 fragment of Macrolactin F was achieved from four main fragments. A hydrotelluration/transmetalation sequence was used to install the E,Z diene present in the molecule, while a hydrozirconation/transmetalation sequence was used to connect two advanced intermediates.     

A concise and enantioselective approach to the total synthesis of (−)-lasubine I

An efficient, enantioselective total synthesis of (−)-lasubine I (1) has been achieved in an overall 8.8% yield from readily available starting materials. The important features of this approach include the creation of stereogenic centers through two sequential highly stereoselective Roush allylborations and the use of S_N2 cyclization and ring-closing metathesis reactions for the construction of the quinolizidine skeleton.     

Stereoselective synthesis of (−)- and (+)-pentenomycins using RCM

An efficient synthesis of enantiopure (−)- and (+)-pentenomycins are described by reductive iodo elimination and ring-closing metathesis (RCM), as the key steps. The first synthesis of the unnatural (+)-isomer is described.     

Toward a synthesis of the antitumor macrolide peloruside A: a chiral pool approach for the C(1)-C(11) segment

Dihydroxylation of the glucose derived α,β-unsaturated lactones 6 and 13 was found to be on the α-face of the pyranolactone ring exclusively. The resulting dihydroxylated compound from 13 has been used in a synthesis of the lactone 4, which corresponds to C(1)-C(11) of peloruside A.     

Studies on the synthesis of apoptolidin A. 1. Synthesis of the C(1)-C(11) fragment

A synthesis of the C(1)-C(11) fragment of apoptolidin A has been accomplished by a convergent route involving the stereoselective glycosidation of 9 and the Suzuki cross-coupling reaction of bromodienoate 7 and the vinylborane generated via chemoselective hydroboration of diyne 6 with diisopinocampheylborane.