A New Cytotoxic Acetogenin from the Seeds of Annona squamosa

A New Annonaceous acetogenin,squamostolide(1),was isolated from the seeds of Annona squamosa.Its structure was elucidated based on spectroscopic methods and comparison with known compounds.It is the first example of Annonaceous acetogenin with each of the two ends of the aliphatic chain bearing a γ-lactone.Thenew compound exhibited cytotoxic activity in vitro against bel-7402 and CNE2 human tumor cell lines.     

Two-directional synthesis of the non-adjacent bis(tetrahydrofuran) core of cis-sylvaticin

Synthesis of the C₂-symmetric, non-adjacent bis(tetrahydrofuran) core of cis-sylvaticin in seven steps and 24% overall yield from (2R,3S)-1,2-epoxy-4-penten-3-ol is reported. A strategy involving assembly of the central 1,4-diol unit by silicon-tethered ring-closing metathesis and subsequent two-directional functionalization, including establishment of the cis/threo stereochemical relationships of the tetrahydrofuran rings by Sharpless asymmetric dihydroxylation/S_N2 cyclization, is employed.     

Four cytotoxic annonaceous acetogenins from the seeds of Annona squamosa

Four new annonaceous acetogenins (ACGs), squamocin-I (1), II (2) and III (3) and squamoxinone-D (4), together with seven known ACGs (5–11), were isolated from the seeds of Annona squamosa. The structures of all isolates were elucidated and characterised by spectral and chemical methods. Compounds 1–4 were evaluated for their cytotoxicities against Hep G2, SMMC 7721, BEL 7402, BGC 803 and H460 human cancer cell lines. Compound 1 exhibited better potent activity than the positive compound and compound 3 shows selectively cytotoxical activity against H460 with IC₅₀ values of 0.0492 μg/ml.     

Total synthesis of murisolins and evaluation of tumor-growth inhibitory activity

Convergent total syntheses of murisolin (1), natural 16,19-cis-murisolin 2, and unnatural 16,19-cis-murisolin 3 were accomplished by asymmetric alkynylation of alpha-tetrahydrofuranic aldehyde with a diyne and Sonogashira coupling with a gamma-lactone segment as the key steps. Stereoisomers of alpha-tetrahydrofuranic aldehyde were synthesized with high optical purity and the asymmetric alkynylation of these with 1,6-heptadiyne proceeded in good yield and with high diastereoselectivity. The cell-growth inhibition profile and COMPARE analysis of the synthetic compounds 1-3 were also investigated.     

Highly functionalized trans-2,5-disubstituted tetrahydrofurans from ribofuranoside templates: precursors to linked polycyclic ethers

Iodoetherification of C5 allylated ribo-furanosides leads to trans-2,5-disubstituted tetrahydrofurans with high selectivity. The application of this reaction to the synthesis of complex polycyclic ethers is illustrated in the preparation of a truncated, tricyclic analog of monensin A.     

Analogues of cytotoxic squamocin using reliable reactions: new insights into the reactivity and role of the α,β-unsaturated lactone of the annonaceous acetogenins

A small library of squamocin analogues has been prepared and screened biologically (cytotoxicity, inhibition of mitochondrial complex I and complex III). To centre diversity on a crucial part of the molecule (i.e., the α,β-unsaturated lactone), an original and reliable lactone opening reaction has been discovered and exploited among other efficient reactions.     

A minimalist NMR approach for the structural revision of mucoxin

In an attempt to revise the structural assignment of mucoxin, and faced with 64 diastereomeric possibilities, we resorted to the synthesis of truncated structures that contained the core stereochemical sites. Twelve stereochemical analogues were synthesized, their (1)H and (13)C NMR spectra were analyzed and four recurring stereochemical trends were distilled from the data. Applying the observed trends to the diastereomeric population pared the possible choices for the correct structure of mucoxin from 64 to 4. Synthesis of these analogues led to the identification of the correct structure of mucoxin.