Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase

• Hui Hong,
• Yuhui Sun,
• Yongjun Zhou,
• Emily Stephens,
• Markiyan Samborskyy and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2016, 12, 2164–2172, doi:10.3762/bjoc.12.206

• Stigmatella aurantiaca [20], further examples have been uncovered in the PKSs for aureothin [21][22], borrelidin [23][24], lankacidin [25][26], neoaureothin [27], etnangien [28], crocacin [29], ebelactone [30] and thiolactomycin [31][32]. Given the close mechanistic analogy between fatty acid synthases and an

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• heterocyclic compounds are produced by a range of actinomycetes and a deeper understanding of their biosynthesis was for a long time hampered by the inability to identify their biosynthetic genes. Those were finally discovered by a comparative genomics approach in which the clusters of thiolactomycin (165

• ), thiotetromycin (166), 834-B1 (167) and Tü 3010 (168) were sequenced and genetically manipulated (Scheme 24a). Gene knockout experiments and heterologous expression of the whole clusters as well as versions devoid of key genes revealed an unprecedented mechanism for heterocycle formation (shown for thiolactomycin

• (165) in Scheme 24b). For thiolactomycin (165), an iteratively acting PKS module produces a tetraketide 169 that contains all backbone carbon atoms of the natural product and which is regioselectively epoxidised at the C4 and C5 carbons by the cytochrome P450 monooxygenase TlmD1 to give 170. The

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• oxathiolanone products by hydrolysis, and the method was employed by Townsend and co-workers in the synthesis of (5R)-thiolactomycin (66, Scheme 23) [51]. Diastereoselective addition of an aldehyde to oxathiolanone 64 affords 65 in 81% yield. Further synthetic manipulations allowed preparation of (5R

• )-thiolactomycin (66) in >99:1 er. 2.2 Electrophilic attack on α-thioorganolithiums Formation of carbon–carbon bonds adjacent to heteroatoms by deprotonation with an organolithium base and subsequent reaction with an electrophile has become an important and versatile method, especially when chiral ligands may be

• of enone 46. Organocatalytic conjugate addition to nitroalkenes 49. Preparation of β-amino acid 54. Sulfur migration within oxazolidine-2-thiones 56. Preparation of thiols 62 by self-regeneration of stereocentres. Synthesis of (5R)-thiolactomycin. Preparation of tertiary thiols and thioethers via α

Novel tetracyclic structures from the synthesis of thiolactone-isatin hybrids

• Renate Hazel Hans,
• Hong Su and
• Kelly Chibale

Beilstein J. Org. Chem. 2010, 6, No. 78, doi:10.3762/bjoc.6.78

• ; hybrids; isatin; tetracycles; thiolactomycin; thiolactone; Introduction Hybrid structures have been found in nature and their synthesis has become a useful drug discovery strategy for new anti-infective agents [1]. Improved pharmacokinetics, therapeutic and toxicity profiles have been reported for

• libraries and concomitantly shortens the time needed to identify potential leads [5]. The focus of this study is on the synthesis of hybrids with monomers derived from natural products thiolactomycin (1) and isatin (2) (Figure 2). The former is a thiolactone antibiotic known for its remarkable selectivity

• against the condensing enzymes of type II fatty acid synthesis which operate in a number of pathogenic organisms [6][7][8]. Synthetic methodologies for 1 and a series of racemic and enantiopure thiolactomycin-based analogues have been reported [9][10][11][12][13][14][15][16]. Of particular interest to

An efficient synthesis of tetramic acid derivatives with extended conjugation from L-Ascorbic Acid

• Biswajit K. Singh,
• Surendra S. Bisht and
• Rama P. Tripathi

Beilstein J. Org. Chem. 2006, 2, No. 24, doi:10.1186/1860-5397-2-24

• . Both solid and solution phase syntheses of such molecules have been reported recently. Thiolactomycin, a clinical candidate for treatment of tuberculosis has led to further explorations in this class. We have recently developed an efficient synthesis of tetramic acids derivatives from L- ascorbic acid