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D‐Ring‐seco‐limonoids (tetranortriterpenoids), such as gedunin and xylogranin B display anti‐cancer activity, acting via inhibition of Hsp90 and/or associated chaperon machinery (e.g. p23). Despite this, these natural products have received relatively little attention, both in terms of an enabling synthetic approach (which would allow access to derivatives), and as a consequence their structure–activity relationship (SAR). Disclosed herein is a generally applicable synthetic route to the BCD ring system of the seco‐D‐ring double bond containing limonoids. Furthermore, cell based assays revealed the first skeletal fragment that exhibited inhibition of the p23 enzyme at a level which was equipotent to that of gedunin, despite being much less structurally complex. The first synthetic route to the BCD ring system of the seco‐D‐ring limonoids has been devised. A synthetic intermediate displayed an equipotent p23 enzyme inhibitory effect to that of the more complex gedunin. [ABSTRACT FROM AUTHOR]

The widely occurring tetranortriterpene natural product gedunin has a well-established range of important biological properties. Although this molecule has received substantial semi-synthetic attention from medicinal chemists, it has not received devoted de novo synthetic attention since it was first isolated in 1960. A key feature of the approach presented herein was the decision to utilize a Robinson annulation reaction, which facilitated the installation of the challenging 7-acetoxy functional group and the completion of the fully functionalized ABC ring system. [ABSTRACT FROM AUTHOR]

Gedunin, first isolated in 1960, displays a remarkable range of biological activity, but has yet to receive dedicated synthetic attention from a ground up construction perspective. Presented herein is a successfully executed approach to the fully functionalized ABC ring system of this challengingly complex natural product. [ABSTRACT FROM AUTHOR]

Herein we describe a direct, multicomponent assembly of 1,5-enynes. The titanocene-catalyzed coupling of an aryl aldehyde, iodoalkyne, and allylsilane enables the convergent and rapid synthesis of this versatile architectural motif in good to excellent yields. [ABSTRACT FROM AUTHOR]

As easy as ABC: David M. Pinkerton, Craig M. Williams, and colleagues at the University of QueENsland Brisbane, Australia, ENgaged in an arduous synthesis campaign that established the first route to the complete ABC ring system of gedunin, a potENt and broadly bioactive natural product. Gedunin was first isolated in 1960, and since thEN has beEN isolated from several natural sources including from the bark of Entandrophragma delevoye, which is pictured on the cover (Photograph: courtesy of Mike Bingham). The structure of gedunin and a scheme highlighting key compounds along the newly developed route are overlaid. More information can be found in their Full Paper by C.   M. Williams et   al. on page   583 in Issue 5, 2017 (DOI: 10.1002/ajoc.201700013). [ABSTRACT FROM AUTHOR]

A three-component coupling reaction of allylsilanes with iodoalkynes and aldehydes leads to 1,5-enynes (IV) and (VIII), which are used as convenient building blocks for the synthesis of iodobenzene (V), cyclobutene (IX), and bicyclo[3.1.0]hexene (X). [ABSTRACT FROM AUTHOR]

Abstract: The Pd[0]-catalyzed Ullmann cross-coupling of o-nitrohaloarenes 1a–e with the brominated heterocycles 2a–f delivers the expected products 3a–j in good to excellent yields. The reductive cyclization of such products, as well as N-acyl derivatives 3k, l, and m, has been investigated and provided the C-3 mono-substituted oxindoles 5a–d, f, g, k, and m, the direct reduction products 4i and j or indole 5l. [ABSTRACT FROM AUTHOR]

The titanocene-catalyzed construction of all-carbon substituted tertiary centers directly from aromatic aldehydes is described. The starting aldehyde behaves as a traceless functionality in the formation of multiple carbon-carbon bonds through consecutive carbon-heteroatom bond activations. The sequential addition of a metal acetylide and a second carbon nucleophile to the dielectrophilic aldehyde enables the construction of symmetrical and unsymmetrical 1,4-diynes in good yields., (© 2011 American Chemical Society)

A SAMPLE OF THE TITLE COMPOUND [SYSTEMATIC NAME: (1aS,2aS,3S,5aS,6aS,7R,7aS,7bS,8R,8aS,10R)-7-hydr-oxy-3-(1-meth-oxy-1-methyl-ethyl)-10-(2-methyl-1-propen-yl)-1a,5a,6a,7,7a,7b,8,8a-octa-hydro-2H-8,2a-(epoxy-methano)phenanthro[2,3-b:6,7-b']bis-oxirene-2,5(3H)-dione], C(23)H(28)O(7), was generated by enanti-oselective synthesis. There are three mol-ecules of the compound in the crystallographic asymmetric unit. Hydrogen bonding between alcohol H atoms and keto groups of adjacent mol-ecules appears to stabilize the structure. The compound is enanti-omerically pure but the absolute configuration could not be determined directly in this study. Accordingly, the illustrated configuration was assigned on the basis of the nature of the chiral nonracemic precursor used in the synthesis.

The enantiomerically pure and readily available metabolites 10-12 have been converted over four simple steps into the epoxyquinol derivatives 22-24, respectively. Compounds 23 and 24 or their immediate precursors have been exploited in efficient total syntheses of (-)-bromoxone (ent-1), (-)-epiepoformin (ent-2), (-)-harveynone (4), (+)-panepophenanthrin (6), and (+)-hexacyclinol (9).

The acetate salts of tambjamines C, E, and F (2-4, respectively), as well as those of the related alkaloids BE-18591 (5) and 6, have been prepared by treatment of bipyrrole aldehyde 16 with the relevant amine in the presence of acetic acid. The 5'-bromo-analogue, 30, of compound 16 has also been prepared and used to obtain the acetate salts of tambjamines G, H, I, and J (8-11 respectively).