The synthesis of (−)-cis- and (−)-trans-crobarbatic acid

The synthesis of both cis- and trans-crobarbatic acid is reported. The five-step sequence proceeds in high yield and with control of both relative and absolute stereochemistry. The key step in the synthesis is the Birch reductive alkylation of a chiral furoic acid which sets the absolute stereochemistry of the products. The stereochemistry of the compounds described was proven unambiguously by X-ray crystallography on one synthetic intermediate and on trans-crobarbatic acid.     

Stereospecific Synthesis of (−)-β-Turmerone and (−)-Bisacurol

The structure of (+)-β-turmerone ((+)- 1a ), a constituent of the rhizomes of Curcuma longa Linn. , and Curcuma xanthorriza, is established as (1′R,6S)-2-methyl-6-(4′-methylenecyclohex-2′-en-1′-yl)hept-2-en-4-one by synthesis of its enantiomer (−)- 1a , and of the corresponding (1′S,6S)-diastereoisomer (+)- 1b as well. In a stereospecific seventeen-step procedure, the monoterpene diols 2a and 2b of well-established configuration are converted into the target compounds (−)- 1a and (+)- 1b , respectively. Moreover, (−)-bisacurol (−)- 3a (II), the enantiomer of another bisabolane sesquiterpene derived from Curcuma xanthorriza, is obtained as a single stereoisomer and shown to be (1′S,6R)-2-methyl-6-(4′-methylenecyclohex-2′-en-1′-yl)hept-2-en-4-ol, the relative configuration at the remaining OH-substituted chiral center C(4) still being unknown.     

Total synthesis of (−)-lentiginosine

A simple and practical synthesis of (−)-lentiginosine 2 with good overall yield has been achieved from the commercially available diethyl d-tartarate. The key steps are a highly stereoselective Grignard reaction on an aldehyde and a Staudinger reduction.     

Stereoselective synthesis of (−)-cytoxazone

A novel stereoselective synthesis of (−)-cytoxazone 1 was achieved via addition of p-methoxyphenylmagnesium bromide to the benzylimine derived from (S)-2,3-O-isopropylidene glyceraldehyde followed by one-step regioselective cyclization of N-Boc amino diol 7.     

Total synthesis of (−)-vindoline

In this full paper, a stereocontrolled strategy for the total synthesis of (?)-vindoline is described. This synthetic route features: 1) rapid construction of the stereochemical center at C19 through a highly diastereoselective vinylogous Mannich addition; 2) tandem Heathcock/aza-Prins cyclization to install rings C and E in vindoline; 3) oxidative transformation of β-ketoester to enone; 4) stereoselective inversion of C4 stereochemistry with triphenylphosphine and carbon tetrabromide followed by Brønsted acid.     

Synthesis of (−)‐Isofagomine

Abstract

1,3‐Dipolar cycloaddition of N‐benzyl nitrone 2 to D‐threo δ‐lactone 15 proceeded with excellent stereoselectivity to provide only one adduct 16. Cycloadduct 16 was subsequently subjected to a sequence of reactions involving rearrangement to γ‐lactone, glycolic cleavage/reduction, protection of the terminal hydroxymethyl group, reduction of the lactone, desilylation/mesylation, and hydrogenolysis of the N‐O bond providing (?)‐isofagomine and its N‐substituted derivatives. The biologic activity of N‐substituted (?)‐isofagomines toward commercially available α‐ and β‐glucosidases, α‐D‐mannosidase, α‐L‐fucosidase, β‐D‐glucuronidase, and β‐D‐galactosidase was tested.     

Total Synthesis of (−)-Rotundone and (−)-epi-Rotundone from Monoterpene Precursors

The first total synthesis of (−)-rotundone has been accomplished from (+)-(R)-limonene and therefore for the first time from an unrelated monoterpene instead of modifying structurally closely related sesquiterpene precursors such as α-guaiene. Challenges such as intermediates with stereocenters prone to epimerization by enolization were overcome by designing a β-methyl-keto route starting from (+)-(R)-limonene which finally gave (−)-rotundone by Nazarov cyclization of a precursor 13a . Diastereomer (−)-epi-rotundone was separated from (−)-rotundone chromatographically. An alternative route from rac-citronellal provided a diastereomer mixture of racemic Nazarov precursor 13 through a TRIP-catalyzed intramolecular aldolization, thus indicating that the Nazarov cyclization precursor 13a is in principle accessible from (−)-(S)-citronellal. The 11-step synthesis from (+)-(R)-limonene with ca. 1 % overall yield confirmed the absolute configuration of (−)-rotundone and provided samples of good olfactory quality.     

Bioinspired Synthesis of (−)-PF-1018

The combination of electrocyclizations and cycloadditions accounts for the formation of a range of fascinating natural products. Cascades consisting of 8π electrocyclizations followed by a 6π electrocyclization and a cycloaddition are relatively common. We now report the synthesis of the tetramic acid PF-1018 through an 8π electrocyclization, the product of which is immediately intercepted by a Diels–Alder cycloaddition. The success of this pericyclic cascade was critically dependent on the substitution pattern of the starting polyene and could be rationalized through DFT calculations. The completion of the synthesis required the instalment of a trisubstituted double bond by radical deoxygenation. An unexpected side product formed through 4-exo-trig radical cyclization could be recycled through an unprecedented triflation/fragmentation.     

A Stereoselective Synthesis of (−)-Endo-Brevicomin

A stereoselective synthesis of (1S,5R,7R) (-)-endo-brevicomin by employing Sharpless kinetic resolution method has been described.     

Total Synthesis of (−)-Glaucocalyxin A

A practically useful method for the formation of the highly oxygenated bicyclo[3.2.1]octane ring system through Mn(OAc)₃-mediated radical cyclization of alkynyl ketones was developed, which opens up a new avenue for the total synthesis of a number of highly oxidized diterpenoids. Application of this method enabled the first total synthesis of (−)-glaucocalyxin A. Other salient features of the synthesis include a highly enantioselective conjugate addition/acylation cascade reaction, a Yamamoto aldol reaction, and an intramolecular Diels–Alder reaction to assemble the A/B ring system.     

Convergent total synthesis of (−)-dactylolide

A convergent total synthesis of (?)-dactylolide is described. Constructing the 2,6-disubstituted exo-methylene THP moiety was achieved by the intramolecular allylation of α-acetoxy ether. The cyclization precursor was prepared from two segments, an alcohol and carboxylic acid derivatives, by esterification followed by reductive acetylation.     

A novel synthesis of (−)-callicarpenal

Callicarpenal, isolated from the leaves of American beautyberry (Callicarpa americana) and Japanese beautyberry (Callicarpa japonica), exhibits significant mosquito bite-deterring activity and repellent activity against ticks and fire ants. The mosquito bite-deterring activity level of callicarpenal was reported to be similar to that of N,N-diethyl-m-toluamide. The novel synthesis of (?)-callicarpenal reported herein was accomplished by starting from (+)-pulegone. In our original approach, a novel Prins-type cyclization based on Meyer–Schuster rearrangement was featured as a key step.     

First total synthesis of (−)-salprzelactone

The first enantioselective total synthesis of (?)-salprzelactone, a seco-norabietane diterpenoid has been accomplished in only three steps. Key transformations of the synthesis include an intermolecular aldol reaction and lactonization.     

Expedient syntheses of indolizidines (−)-167B and (−)-209D

Indolizidine alkaloids (−)-167B and (−)-209D were synthesized via an expedient route using hydroacylation and amination.     

Synthesis of the scalemic form of alkaloid (−)-dipthocarpamine

The scalemic form of active alkaloid (−)-dipthocarpamine was synthesized by asymmetric oxidation ofN-isopropyl-N′-(methylthiohexyl)urea with hydrogen peroxide in the presence of vanadium(IV) complexes with chiral Shiff's bases. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 564–565, March, 2000.     

Conformational study of α-arylethylamides of (−)-camphanic acid

The absolute conformation and configuration of diastereomeric amides (4A,B–6A,B) of (1S,3R)-camphanic acid (lactone of 1-hydroxy-2,2,3-trimethylcyclopentan-1,3-dicarboxylic acid, (−)-camphanic acid 9) with α-arylethylamines 1–3 are deduced from ¹H NMR data and MM2 calculations. The α-arylethyl group in diastereomers A and B adopt nearly opposite absolute conformations, stabilized by hydrogen bonding in the syn-oriented O–C(1)–C(6)–N–H unit, and repulsive interaction between the 1′C–Me group and the amide CO group. The absolute configuration (1′S) is assigned to the 4A–6A diastereomers, and the (1′R)-configuration to the 4B–6B diastereomers; this assignment is confirmed by the preparation of 4A and 5A from enantiomerically pure (1′S)-α-arylethylamines 1 and 2, respectively. These results also enabled the assignment of pro-R (H_R) and pro-S (H_S) protons in the benzyl derivative 7.     

Synthesis and some transformations of (−)-carveol

Reduction of the oxo group in (?)-carvone with LiAlH₄, NaBH₄, and (i-Bu)₂AlH was performed. It was found that the reduction with the system CeCl₃ · 7 H₂O-NaBH₄ in methanol at 20°C is the most practical procedure for the synthesis of (?)-carveol. Solvolysis of (?)-carvyl methanesulfonate gave products of S_N2 and S_N2′ replacement of the methylsulfonyloxy group, the latter slightly prevailing. Overman rearrangement of (?)-carveol resulted in the formation of the corresponding trichloroacetamide derivative, and intramolecular iodoetherification of the title compound afforded 6-iodomethyl-2,6-dimethyl-7-oxabicyclo[3.2.1]oct-2-ene.     

Enantioselective Synthesis and Racemization of (−)-Sinoracutine

Sinoracutine is a recently isolated alkaloid with unusual stereochemical and biological properties. It features an unprecedented tetracyclic 6/6/5/5 skeleton that bears an N-methylpyrrolidine ring fused to a cyclopentenone. Interestingly, both enantiomers of sinoracutine have been independently isolated from the same plant, yet the molecule does not appear to occur as a racemate. Here, we present a short synthesis of (−)-sinoracutine that relies on a highly diastereoselective Pauson–Khand reaction and a Mandai–Claisen reaction to install the quaternary stereocenter. Our work establishes the absolute configuration of the levorotatory isomer and suggests that the optical purity of sinoracutine varies in nature due to its gradual racemization. Experimental evidence supports this proposal, and a plausible mechanism for the racemization is provided.     

The total synthesis of (−)-indolactam I

The first total synthesis of (−)-indolactam I (1) is reported. An efficient synthetic route was established to furnish the natural product in 8 steps. This strategy employed a copper-catalyzed amino acid arylation, peptide coupling, and Lewis acid-mediated macrocyclization to yield 1 from readily available building blocks. In addition, the cell growth inhibition activity of the natural product was examined through assays with the K562 leukemia cell line.     

Enantioselective synthesis of (−)-γ-jasmolactone

The title compound was prepared in seven steps starting from the commercially available 4-ketopimelic acid. The key step features an enantioselective lactonization promoted by PPL.