Total synthesis of solandelactones E and F, homoeicosanoids from the hydroid Solanderia secunda

Asymmetric total syntheses of solandelactones E and F confirmed that hydroxyl configuration at C11 in these oxylipins had been misassigned and that the stereochemistry at this center should be reversed. Key steps in the synthesis involved a Nagao asymmetric acetate aldol reaction, a directed Simmons-Smith cyclopropanation, a Holmes-Claisen rearrangement to establish the unsaturated octalactone, and a Nozaki-Hiyama-Kishi coupling to connect two major fragments at C11-C12.     

Amphidinolide B: asymmetric synthesis of a C7-C20 synthon

[reaction: see text] An asymmetric synthesis of a C(7)-C(20) synthon of amphidinolide B is described. The synthesis entails the construction of C(7)-C(13) and C(14)-C(20) fragments and makes extensive use of catalytic asymmetric bond constructions to establish the requisite stereochemical relationships. Fragment coupling proceeds by Suzuki cross-coupling and installs the trisubstituted diene unit that is among amphidinolide B's defining structural features.     

An efficient synthesis of the C27–C45 fragment of lagunamide A,a cyclodepsipeptide with potent cytotoxic and antimalarial properties

An efficient and stereoselective synthesis of the entire C27–C45 moiety of lagunamide A has been achieved from 1-[(4S)-4-benzyl-2-thioxothiazolidin-3-yl]propan-1-one in six steps with 22% overall yield. The key step in the synthesis is an asymmetric acetal aldol reaction featuring the enantioselective addition of a chiral thiazolidinethione-derived titanium enolate to an acetal to establish the stereochemistry at C39.     

Formal synthesis of 6-deoxyerythronolide B

[reaction: see text] The enantioselective synthesis of the carbon skeleton of 6-deoxyerythronolide B has been achieved in 23 linear steps from propionaldehyde. The synthesis relies on an iterative approach employing an asymmetric acyl-thiazolidinethione propionate aldol reaction to establish eight of nine stereogenic centers. The remaining stereogenic center at C6 was set through a Myers alkylation employing a complex alkyl iodide.     

Synthesis of Enantiopure C3‐Symmetric Triangular Molecules

An asymmetric synthesis of C ₃‐symmetric triangular macrocycles is reported. 1‐Methylsulfonyl‐4‐(4‐vinylphenyl)‐1,2,3‐triazole undergoes a rhodium(II)‐catalyzed cyclotrimerization to establish an enantiopure C ₃‐symmetric triangular macrocycle motif. This method can be applied to the synthesis of an enantiopure hydrocarbon, which owes its chirality to asymmetric distribution of H/D atoms on the benzene rings.     

Total Syntheses of (−)‐Isoschizogamine and (−)‐2‐Hydroxyisoschizogamine

Total syntheses of (?)‐isoschizogamine and (?)‐2‐hydroxyisoschizogamine are described. The synthesis employs two asymmetric Michael additions to establish chiral centers at C7 and the quaternary carbon C20. Regioselective reduction of the methylthioiminium cation rather than the enamine generates an isoschizogamine‐type pentacyclic skeleton. Acidic hydrolysis of the isoschizogamine‐type intermediate in the absence of oxygen provides natural (?)‐isoschizogamine. Conducting the reaction in the presence of oxygen leads to a multistep oxidative hydrolysis cascade that affords unnatural (?)‐2‐hydroxyisoschizogamine.     

Enantioselective synthesis of apoptolidinone: exploiting the versatility of thiazolidinethione chiral auxiliaries

An efficient, enantioselective synthesis of apoptolidinone has been completed, demonstrating the versatility of thiazolidinethione auxiliaries. Three propionate aldol additions and two asymmetric glycolate alkylations function to establish 8 of the 12 stereogenic carbon centers. A cross-metathesis reaction is utilized to assemble the C1-C10 trieneoate fragment and the C11-C28 polypropionate region of the molecule.     

Total synthesis of akuammiline alkaloid (+)-strictamine

An asymmetric total synthesis of the akuammiline alkaloid (+)-strictamine is described. The key steps of the synthetic route involve an improved Johnson-Claisen rearrangement to facilitate the formation of the challenging C15–C20 linkage and the (E)-alkene side chain, intramolecular nucleophilic substitution cyclization to establish the E ring and diastereoselective Brown hydroboration of the terminal alkene to introduce the C16 stereocenter.     

Synthetic studies toward amphidinolide B1: synthesis of the C9-C26 fragment

[reaction: see text] The synthesis of the C9-C26 portion of amphidinolide B1 is described. A Fleming allylation followed by elimination was employed for the construction of the C13-C15 diene portion. Sharpless asymmetric dihydroxylation was utilized for regioselective functionalization of a styrene-derived alkene, in the presence of the C13-C15 diene functionality. A highly diastereoselective aldol reaction was developed to establish the C18 stereochemistry.     

Total synthesis of (+)-crocacin D

[structure: see text] The total synthesis of (+)-crocacin D is described. The convergent asymmetric synthesis relies on the use of a Stille cross-coupling between an (E)-vinyl stannane with an (E)-vinyl iodide to establish the (E,E)-dienamide moiety followed by a mild and efficient copper-catalyzed coupling between (+)-crocacin C and a (Z)-vinyl iodide to establish the challenging (Z)-enamide function.     

The first asymmetric total syntheses and determination of absolute configurations of xestodecalactones B and C

The first efficient asymmetric total syntheses of xestodecalactones B and C have been accomplished in 10 steps with an overall yield of 22 and 20.2%, respectively. The key steps involve the utility of Evans oxazolidinone-mediated syn-aldol condensations to establish the C-9 configuration and the macrolide ring formation by intramolecular acylation. The absolute configurations of xestodecalactones B and C have been determined via these syntheses.     

Synthesis of the C22-C37 segment of prorocentin

The synthesis of the C22-C37 segment of prorocentin, isolated from the dinoflagellate Prorocentrum lima, was achieved. Because the relative stereochemical relationship between C26 and other stereocenters (C28/C31/C32 established as R*/R*/R*) in the C22-C37 region of natural prorocentin has not yet been determined, both epimers at C26 of the C22-C37 segment were selectively constructed. The synthesis was based on a 5-exo epoxide ring opening reaction to form an oxolane (E-ring), Brown asymmetric methallylation to install the C26-stereocenter, acryloylation of the resulting alcohol, and ring-closing olefin metathesis to establish the Z-olefin at C23/C24.     

Approach to the synthesis of dolabelides A and B: fragment synthesis by tandem silylformylation-crotylsilylation

[structure: see text] A synthesis of the C(15)-C(30) fragment of Dolabelides A and B has been achieved. The recently developed asymmetric silane alcoholysis and tandem silylformylation-crotylsilylation reactions were used as the key steps to establish the C(23)-C(27) 1,5-syn-diol. In addition, the flexibility of this methodology has been demonstrated with an efficient synthesis of the C(24)-C(25) trisubstituted olefin.     

A versatile new catalyst for the enantioselective isomerization of allylic alcohols to aldehydes: scope and mechanistic studies.

A new planar-chiral bidentate phosphaferrocene ligand (2) has been synthesized and structurally characterized. The derived rhodium complex, [Rh(cod)(2)]BF(4), serves as an effective catalyst for asymmetric isomerizations of allylic alcohols to aldehydes, furnishing improved yields, scope, and enantioselectivities relative to previously reported methods. The catalyst is air-stable and can be recovered at the end of the reaction. Mechanistic studies establish that the isomerization proceeds via an intramolecular 1,3-hydrogen migration and that the catalyst differentiates between the enantiotopic C1 hydrogens.     

Enantioselective synthesis of apoptolidin sugars

[structure: see text] The de novo synthesis of the C9 and C27 sugar subunits (2) and (3), respectively, of the potent antitumor agent, apoptolidin, has been accomplished. A titanium tetrachloride-mediated asymmetric anti glycolate aldol addition was utilized to establish the 4' and 5' stereogenic centers of each of the three monosaccharides. Elaboration of the aldol adducts efficiently provided the three sugar units. A beta-selective glycosidation completed the construction of the C27 disaccharide.     

An aldol approach to the synthesis of the EF fragment of spongistatin 1

A synthesis of the C29-C51 fragment of spongistatin 1, containing the E and F rings, has been completed. The approach relies on four diastereoselective aldol additions and an asymmetric glycolate alkylation to establish eight of the eleven stereogenic centers. The intact chlorodiene side chain was appended by a Lewis acid catalyzed addition of an allylstannane to an epoxy enol ether.     

Asymmetric approach towards the total synthesis of (+)-actinopyllic acid

This paper describes our efforts towards the asymmetric total synthesis of (+)-actinophyllic acid. Starting from the chiral oxazolidinone 9, an azocino [4,3-b]indolyl intermediate (5) possessing the A/B/C ring system and the C16 quaternary stereogenic center of actinophyllic acid has been synthesized. Key steps include a LHMDS-promoted condensation to establish the critical C2–C16 bond and a successive four-step transformation to assemble the eight-membered C-ring of the target molecule.     

Born-Oppenheimer symmetry breaking in the C state of NO2: importance of static and dynamic correlation effects

A systematic theoretical treatment is performed with highly correlated ab initio theoretical methods to establish the structural nature of the C state of NO2. We predict the C state to have an asymmetric structure (point group C(s)). Spin-restricted and spin-unrestricted configuration interaction (CISD), coupled cluster [CCSD and CCSD(T)], multireference complete active space self-consistent field (CASSCF), and internally contracted multireference configuration interaction (ICMRCI) methods were used in conjunction with very large correlation-consistent polarized valence zeta cc-pVXZ and aug-cc-pVXZ [X = T, Q, 5] basis sets. The asymmetric C 2A' state is predicted to lie T(e) = 47.5 kcal/mol (2.06 eV, 16,600 cm(-1)) above the X 2A1 state at the aug-cc-pV5Z/UCCSD(T) level of theory, with T0 = 46.0 kcal/mol (2.00 eV, 16,100 cm(-1)), in good agreement with the experimental values of 46.77 kcal/mol (2.028 eV, 16,360 cm(-1)) by Weaver and 46.42 kcal/mol (2.013 eV, 16,234 cm(-1)) by Aoki. The symmetric structure (in C(2v) symmetry) with re(NO) = 1.274 A and theta(e) (ONO) = 109.9 degrees is a transition state between the two equivalent asymmetric (in C(s) symmetry) structures and is located only 1.53 kcal/mol (0.066 eV, 540 cm(-1)) above the asymmetric structure. The asymmetric structure is predicted to have structural parameters r(e)(NOl) = 1.489 A, r(e)(NOs) = 1.169 A, and theta(e)(ONO) = 109.7 degrees with the same method, aug-cc-pV5Z/UCCSD(T). The averaged NO bond distance is 1.329 A, and the difference between the two NO bond distances is 0.320 A. The three harmonic vibrational frequencies for the C 2A' state are 1656 (in-phase stretch), 759 (bend), and 378 (out- of-phase stretch) cm(-1). While these theoretical results further corroborate the previous predictions concerning the asymmetric nature of the C state, there remains discrepancy between the theoretical and experimental symmetric stretching mode omega1 (1656 and 923 cm(-1), respectively). It is possible, however, that this disagreement could be resolved by a reassignment of the corresponding lines in the experimental spectrum, though additional vibronic simulations of the spectrum are required to confirm this proposition.     

Synthetic efforts toward the C22-C36 subunit of halichondrin B utilizing local and imposed symmetry

The C22-C34 portion (2) of halichondrin B was synthesized from meso-symmetric bis-silyl protected cyclopentenediol (7) in 20 steps and 7% overall yield. This was accomplished through a two-directional synthesis/terminus differentiation strategy that proceeded via achiral, meso-symmetric intermediates for eight steps and employed a Pd(0)-mediated asymmetric double cycloetherification to establish both tetrahydropyran rings. [Structure: see text]     

Total synthesis of (-)-pironetin

[structure: see text] The asymmetric total synthesis of pironetin, a compound that shows plant growth regulatory activity, immunosuppressive as well as a remarkable antitumoral activity, is described. The approach involves the use of three very efficient Evans oxazolidinone-mediated syn-aldol condensations, a high-yielding coupling between lithium acetylide ethylenediamine complex and a tosylate followed by methylation, and selective reduction to establish the C12-C13 (E) double bond.