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26 November 2006 8,792 views 5 Comments


Fecik, Lakshmanan, Salomon and Sherman. JOC, 2006, ASAP. DOI: 10.1021/jo062047u.

An interesting paper, this ‘un. The group are targeting the two macrolides; narbonolide and it’s big brother, pikromycin, using a biotransformation to perform the glycosidation and oxidation. However, they’ve got to make narbonolide first!


As shown in the retro, the linear molecule is constructed through a pair of Evan’s aldols. The synthesis of the constituents was not discussed, primarily because this is a second generation synthesis. These earlier works were generally found wanting in the macrocyclisation, but Fecik and his team excelled, with a 90% yield. This then allowed them to proceed to the biotransformation.


This must have been a fairly scary step; the group did the reaction on a 4mg scale, which a reasonable amount to submit to such an advance precursor, especially considering the lack of presidence. The experimental details mean nothing to me; lots to learn, as ever:

“A concentrated spore stock (10 μL) of the Streptomyces venezuelae pikAI deletion mutant BB138 was used to inoculate 50 mL of ATCC172 media (10 g of glucose, 20 g of soluble starch, 5 g of yeast extract, 5 g of NZ amine type A, and 1 g of CaCO3 per 1 L of H2O) in a 250 mL baffled flask and incubated at 30 °C for 2 days with shaking. This seed culture (5 mL) was used to inoculate fresh ATCC172 media (50 mL) containing narbonolide (1, 4 mg in 400 μL EtOH) or EtOH (400 μL) and incubated at 30 °C for 3 days with shaking…”

No yield was given for the transformation, just a HPLC trace, showing both SM and product.


Overall, a very competent macrolide synthesis, and a nice application of a biological transformation (that keep you happy ddd??!:))

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  • ddd says:

    :)) stop picking on me lol, this is an international website with thousands of people, I am embarrased….

    last step is interesting though. It looks like pretty standart culture technique and pretty easy to perform if you have incubator/shaker. And it is very easy to generate that gene deletion mutant, bio people do it on daily basis

  • ddd says:

    standart should be standard, sorry for that guys

  • European Chemist says:

    Apologies accepted, ddd :-D :-D

  • HOMO-LUMO says:

    That’s why some people is in the directed evolution of enzymes bussiness

  • Ochemist says:

    The last procedure reminds me those famouse alchemist recipes