James D. White

A New Catalyst for the Asymmetric Henry Reaction: Synthesis of β-Nitroethanols in High Enantiomeric Excess

A new chiral tetrahydrosalen ligand has been designed and synthesized from cis-2,5-diaminobicyclo[2.2.2]octane. The complex generated in situ by the interaction of the ligand with (CuOTf)(2)·C(6)H(5)CH(3) was an efficient catalyst for the asymmetric Henry reaction, producing nitroaldol products in high yield and good stereoselectivity. Henry reactions catalyzed by this tetrahydrosalen-Cu(I) complex led to syntheses of β-adrenergic blocking agents (S)-toliprolol, (S)-moprolol, and (S)-propanolol.

Absolute configuration of curacin A, a novel antimitotic agent from the tropical marine cyanobacterium Lyngbya majuscula

Curacin A is a structurally novel antimitotic agent isolated from the Caribbean cyanobacterium Lyngbya majuscula. Its planar structure has been previously determined from a spectroscopic investigation. Here, we define the complete relative and absolute configuration of curacin A by comparison of products obtained from chemical degradation of the natural product with the same substances prepared by synthesis. Curacin A is shown to have 2R, 13R, 19R, 21S absolute configuration.

The structure of leptosphaerin

Abstract The structure and relative configuration of leptosphaerin, a metabolite of the marine ascomycete Leptosphaeria oraemaris (Linder) was established as 2 by spectral analysis and elimination of an alternative structure 1 through synthesis.

Total synthesis and biological evaluation of (+)-kalkitoxin, a cytotoxic metabolite of the cyanobacterium Lyngbya majusculaElectronic supplementary information (ESI) available: 1H NMR spectrum of synthetic (+)-kalkitoxin in C6D6. See http://www.rsc.org/suppdata/ob/b4/b404205k/

+-Kalkitoxin, a metabolite of the marine cyanobacterium Lyngbya majuscula, was synthesized from (R)-2-methylbutyric acid, (R)-cysteine, and (3S, 4S, 6S)-3,4,6-trimethyl-8-(methylamino)octanoic acid. A key step in the synthesis was installation of the anti,anti methyl stereotriad by means of a tandem asymmetric conjugate addition of an organocopper species to an alpha,beta-unsaturated N-acyl oxazolidin-2-one followed in situ by alpha-methylation of the resultant enolate. The thiazoline portion of kalkitoxin was assembled by titanium tetrachloride catalyzed cyclization of a vinyl substituted amido thiol.

The synthesis and absolute configuration of (+)-leptosphaerin

Abstract A synthesis of (+)-leptosphaerin (1), a metabolite of the marine ascomycete Leptosphaeria oraemaris (Linder), was accomplished from (R)-glyceraldehyde by a route that confirms the structural assignment and establishes the absolute configuration of 1 as (4S,5R).

Structure, Sythesis and Absolute Configuration of Leptosphaerin, a Metabolite of the Marine Ascomycete Leptosphaeria oraemaris.

A structure 3 erroneously deduced for the marine fungal metabolite leptosphaerin on the basis of spectroscopic evidence and an ambiguous x-ray analysis was disproved by synthesis. An alternative formulation 1, including its absolute configuration, was confirmed by a stereospecific synthesis that began with condensation of the acetonide 8 of (R)-glyceraldehyde with the dianion from(Z)-N-methyl-2-benzyloxy-3-phenylthioacrylamide (34). The derived α-hydroxy lactone 43 was converted to the enamide moiety of leptosphaerin via decomposition of azidolactone 45. Leptosphaerin is thus the γ-lactone of (4S,5R)-2-acetamido-4,5,6-trihydroxy-2-hexenoic acid and, as such, is a derivative of a D amino hexose.

Total synthesis of solandelactones A, B, E, and F exploiting a tandem Petasis-Claisen lactonization strategy.

Solandelactones A, B, E, and F were synthesized using Nozaki-Hiyama-Kishi coupling of iododiene 13 with aldehydes 14 and 99 obtained by oxidation of alcohols 92 and 94. Key steps in the synthesis of 92 and 94 were (i) a Nagao asymmetric acetate aldol reaction of aldehyde 77 with thionothiazolidine 78 to set in place an alcohol that becomes the (7 S) lactone center of solandelactones, (ii) a Simmons-Smith cyclopropanation of 80 directed by this alcohol, and (iii) Petasis methylenation of cyclic carbonate 90 in tandem with a Claisen rearrangement that generates the octenalactone portion of solandelactones. Synthesis of solandelactones A, B, E, and F confirmed their gross structure and absolute configuration at C7, 8, 10, and 14 but showed that alcohol configuration at C11 must be reversed in pairs, A/B and E/F, from the previous assignment made to these hydroid metabolites. Thus, solandelactones A and B are correctly represented by 2 and 1, respectively, whereas solandelactones E and F are 6 and 5. A biogenesis of solandelactones is proposed for these C 22 oxylipins that parallels a hypothesis put forward previously to explain the origin of C 20 cyclopropane-containing algal products.

Configurational and conformational analysis of highly oxygenated pyrrolizidines: definitive identification of some naturally occurring 7a-epi-alexines

Abstract The NMR spectra of a number of naturally occurring alexines (tetrahydroxylated pyrrolizidine alkaloids) are analyzed and the consequences of changes in the configuration on the conformation of these bicyclic systems discussed. Unambiguous syntheses of australine (7-epi-alexine) and of 7,7a-epi-alexine have now unequivocally established the structures of two natural products isolated from Castanospermum australe which were insecure due to erroneous NMR data. Chemical shift parameters are unreliable as a method of comparing different samples of identical compounds; however, 1H–1H three bond coupling constants (3JHH) provide easy direct comparison between samples and allow assignments of both the relative configurations for the ring protons and the conformation of the pyrrolizidine framework.

(2S,3R)-1,2-epoxy-3-butanol. A useful synthon for the preparation of chiral 1,2-diols.

Enantioselective epoxidation of 3-butene-2-ol in the presence of D-(-)-tartrate gave (2S,3R)-1,2-epoxy-3-butanol, which was employed in chiral syntheses of 2,5-dideoxyribose and a segment of the ionophoric antibiotic boromycin.

A Novel Synthesis of (−)-Huperzine A via Tandem Intramolecular Aza-Prins Cyclization–Cyclobutane Fragmentation

The acetylcholinesterase inhibitor (-)-huperzine A was synthesized from (S)-4-hydroxycyclohex-2-enone in 17 steps by a route that involved two cyclobutane fragmentations. The first of these employed a retro-aldol cleavage to generate the α-pyridone ring of huperzine A, and the second invoked a novel intramolecular aza-Prins reaction in tandem with stereocontrolled scission of a cyclobutylcarbinyl cation to create the aminobicyclo[3.3.1]nonene framework of the natural alkaloid.