Labile natural products

How do we decide whether to separate a mixture by gc or hplc In gc, mixtures are examined in the vapour phase, so that we have to be able to form a stable vapour from our mixture, or convert the substances in it to derivatives that are thermally stable. Only about 20% of chemical compounds are suitable for gc without some form of sample modification the remainder are thermally unstable or involatile. In addition, substances with highly polar or ionisable functional groups often show poor chromatographic behaviour by gc, being very prone to tailing. Thus hplc is the better technique for macromolecules, inorganic or other ionic species, labile natural products, pharmaceutical compounds and biochemicals. 

HPLC is limited by sample volatility or thermal stability. It is also ideally suited for the separation of macromolecules and ionic species of biomedical interest, labile natural products, and a wide variety of other high molecular weight and/or less stable compounds (see Section 15.12). 

Some of the most usefiil materials for the chromatography of labile natural products are the fairly inert polymers of carbohydrates. Polysaccharides can be crosslinked to produce three-dimensional networks (see Fig. 7). These polymeric materials can then be formed into beads. 

This highly convergent synthesis amply demonstrates the utility of Evans s asymmetric aldol and alkylation methodology for the synthesis of polypropionate-derived natural products. By virtue of the molecular complexity and pronounced lability of cytovaricin, this synthesis ranks among the most outstanding synthetic achievements in the macrolide field. 

The provocative initial biological activities reported for PatA, primarily the 20,000-fold difference in toxicity toward cancer cells (P388) versus a quiescent cell line (BSC) (Northcote et al, 1991), led us to undertake a total synthesis of this natural product that would ultimately enable detailed mode of action studies. We envisioned the synthesis and subsequent union of three principal fragments, namely, enyne acid 4, /1-lactam 10, and dienylstannane 14 (Fig. 14.1). A crucial aspect of this plan was a late-stage Stille coupling to append the expected labile trienyl... 

Electron-rich alkenes are the more reactive jr-bond snbstrates towards epoxidation by the electrophilic dioxiranes Some typical examples of these oxidations are snm-marized in Scheme 2. Since the resnlting epoxides are nsnally hydrolytically and ther-molytically qnite labile, snch oxidations are best carried ont with isolated dioxiranes. For example, the 8,9 epoxide of the well-known aflatoxin B, postnlated as potent carcinogen in the oxidative metabolism of this natural product, escaped numerous efforts to prepare it by conventional epoxidations because of its sensitivity towards hydrolysis . The synthesis of this labile epoxide was readily accomplished by employing a solution of the isolated DMD at room temperature (equation 2), and its mutagenicity unequivocally... 

In view of the very labile nature of the products of 1,3-addition to the nitrone group, the claim5,76 that 90c reacts with acetyl chloride to form a fairly stable adduct (115), which undergoes further nucelophilic substitution (forming 116) requires further investigation. 

The importance of color to final perceived quality of food products, combined with the labile nature of chlorophyll derivatives, has perpetuated numerous efforts to preserve native green vegetable appearance. Fishenbach... 

Color production is the primary characteristic of the Flaillard reaction, yet surprisingly little is known about any chromophores present (j ). In view of the labile nature of at least some of the browning products, rapid separation of these complex mixtures with minimal exposure to heat and air is necessary. High-performance liquid chromatography promised to provide almost the ideal answer. 

My co-worker H. Lagally showed that the thermal decomposition of Fe(CO)4I2 afforded successively Fe(CO)2I2, Fe(CO)2I, and CO-free Fel. For these decomposition products of Fe(CO)4I2 a polymeric structure with iodine bridges is postulated. A study of the reaction FeI2 + 4 CO Fe(CO)4I2, also in collaboration with Lagally, further established the metastable or labile nature of iron carbonyl halides (63). 

One common structural element of natural products exhibiting antibiotic properties is the incorporation of a (3-lactam moiety. This structural unit is somewhat labile. Because ozonation is generally recognized as a mild, clean, and selective method for oxidation of a compound, it can be considered an attractive synthetic transformation during the synthesis of antibiotics and their analogues. 

The first example of a chiral-auxiliary-induced [2+2] cycloaddition between 02 and oxazolidinone-functionalized enecarbamates, which proceeds with complete diastereoselectivity as a result of steric repulsions, has been reported to afford 57 <02JACS8814>. The optically active enecarbamates bearing Evans chiral auxiliary were photooxygenated at -35 °C with 5,10,15,20-tetrakis(pentafluorophenyl)porphine (TPFPP) as sensitizer and an 800 W sodium lamp as light source. The dioxetanes 57 were obtained exclusively, but they readily decomposed at room temperature to the expected carbonyl products because of their thermally labile nature. The absolute configuration of the dioxetanes 57 was established by reduction to the corresponding diols with L-methionine. 

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