Aromachemical screen update

[MFernflower]

I got a reply back from the company

@mattodd seems like they won't be able to provide the compounds Pro Bono but they are interested nonetheless!

@wwjvdsande or @bebi78 could try and see what of the list they can order and ship using research funding?!

https://shop.perfumersapprentice.com/ is there main website

[bebi78]

@MFernflower @mattodd @wwjvdsande I checked the prices for the compounds of the list (lowest available amounts of Perfumers Apprentice, without shipping costs, see below). I think we don't need all of them and ´´high-priced´´ hexadecanolide, for example, can be omitted in my opinion. But at least, bisabolene and ambrettolide should be considered for ordering because of their biological activities. Galaxolide (4 ml): 3 USD Calone 1951 (8 g): 11 USD Javanol (4 ml): 11.25 USD Ambrettolide (4 ml): 7.75 USD Maritima (4 ml): 4.75 USD Ambroxane crystals (8 g): 15 USD Habanolide (4 ml): 3 USD Globanone (4 ml): 3 USD Fructalate (4 ml): 3.50 USD Scentenal (4 ml): 3 USD Bisabolene (4 ml): 5.25 USD Indolarome (8 g): 8 USD Hexadecanolide (4 ml): 15.25 USD Total: 93.75 USD

[MFernflower]

We could probably omit Hexadecanolide, Maritima, Galaxolide and Fructalate to be honest! @OpenSourceMycetoma/corecontrib

Updated list then:

Calone 1951 crystals (8 g): 11 USD Javanol (4 ml): 11.25 USD Ambrettolide (4 ml): 7.75 USD Ambroxane crystals (8 g): 15 USD Habanolide (4 ml): 3 USD Globanone (4 ml): 3 USD Scentenal (4 ml): 3 USD Bisabolene (4 ml): 5.25 USD Indolarome crystals (8 g): 8 USD

[bebi78]

@MFernflower @mattodd @wwjvdsande OK. I will order these compounds from Perfumers Apprentice, and maritima because I like the combi of terpene with pyridine.

[MFernflower]

@bebi78 If you have a chance could you upload a graphic or spreadsheet of all the molecules you purchased?

[bebi78]

@MFernflower Here is the word file with the structures of the ordered compounds.

PerfumersApprentice.docx

[MFernflower]

@dmitrij176 to add these compounds to master list when time permits

[mattodd]

Actually I think we need to spread the load a little here. @dmitrij176 has been adding a fair few compounds to the Master List recently. Could one of you @MFernflower or @bebi78 perhaps take a turn? The fields should be self-explanatory, and the MyOS numbering system is hopefully clear?

[MFernflower]

@mattodd I don't know if I even have write access to the master list but my apologies for assigning the work as I did!

On Wed, Mar 9, 2022, 3:59 PM Mat Todd @.***> wrote:

Actually I think we need to spread the load a little here. @dmitrij176 https://github.com/dmitrij176 has been adding a fair few compounds to the Master List recently. Could one of you @MFernflower https://github.com/MFernflower or @bebi78 https://github.com/bebi78 perhaps take a turn? The fields should be self-explanatory, and the MyOS numbering system https://github.com/OpenSourceMycetoma/MycetOS-Tech-Ops/wiki/The-Molecule-Numbering-Convention is hopefully clear?

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[mattodd]

Yes, you should be able to edit the Master List.

[MFernflower]

@mattodd @bebi78 I entered the data - fingers crossed I did not make any mistakes

[bebi78]

@MFernflower @mattodd @wwjvdsande I'm sorry, there is a problem with the order. Because Perfumer's Apprentice only accepts orders with advance payment, I can't order it because our university does not order anything with advance payment. Any suggestions?

[MFernflower]

@bebi78 there are other suppliers for aroma compounds perhaps they could step in? Could always try to contact perfumer's apprentice via email?

On Fri, Mar 11, 2022, 7:45 AM bebi78 @.***> wrote:

@MFernflower https://github.com/MFernflower @mattodd https://github.com/mattodd @wwjvdsande https://github.com/wwjvdsande I'm sorry, there is a problem with the order. Because Perfumer's Apprentice only accepts orders with advance payment, I can't order it because our university does not order anything with advance payment. Any suggestions?

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[bebi78]

@MFernflower Yes, I wrote an email to Perfumer's Apprentice, but seems to be no other way than advance payment.

[MFernflower]

Calone 1951, Habanolide and Scentenal might be available from the manufacture themselves as they have a sample program

They also make muscone and some other terpenoid products too

https://www.firmenich.com/company/contact-us

@bebi78

[bebi78]

@MFernflower Good idea. Maybe these companies like Firmenich, IFF and Givaudan, which produce these fragrances, can provide Wendy with free samples, because only 2-3 mg or 1 mL are needed.

[MFernflower]

@bebi78 I don't have an institutional email so probably best for somebody who does to reach out to the chemical companies who make these molecules on an industrial scale

Also with regard to quantities: Perfume chemists don't normally use the small amounts that drug chemists use so the quantities would be more like 100 mg of the solid products and 500 to 1500 μL of liquid products

[MFernflower]

@bebi78 @mattodd I'm going to try to reach out to Firmenich - Wish me luck!

[bebi78]

@MFernflower @mattodd Thanks and good luck! I will contact Givaudan next week by mail or phone for free samples of ambrettolide, javanol and bisabolene. It took some time but I found their list of fragrances and ingredients (see below) with numerous interesting compounds such as safranal or jasmone.

giv-fb-fragrance-ingredients-sustainability-profile-catalogue.pdf

[MFernflower]

@bebi78 if you could make up a table of things you find interesting from Givaudan that'd help me alot - I think via phone might be better option I'm still waiting on Firmenich to awnser email but I digress

On Sat, Mar 12, 2022, 7:51 AM bebi78 @.***> wrote:

@MFernflower https://github.com/MFernflower @mattodd https://github.com/mattodd Thanks and good luck! I will contact Givaudan next week by mail or phone for free samples of ambrettolide, javanol and bisabolene. It took some time but I found their list of fragrances and ingredients (see below) with numerous interesting compounds such as safranal or jasmone.

giv-fb-fragrance-ingredients-sustainability-profile-catalogue.pdf https://github.com/OpenSourceMycetoma/Adjuvant-Screen/files/8237621/giv-fb-fragrance-ingredients-sustainability-profile-catalogue.pdf

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[wwjvdsande]

@MFernflower @bebi78 sorry for not answering before. I was away for a week. Our university also does not pay in advance. But the options you discussed by looking at other companies might work! Will be a lot of fragrances in our assay I assume. I need to take that also in consideration when I perform the test. With some of the plant extracts with fragrances I tested before we sometimes also had volatile compounds in them which could influence the MICs of other compounds.

[bebi78]

@wwjvdsande Thanks. I don't think that every compound will be active. If there are two-three hits in this series of fragrances with activity at 20 µM and 100 µM it would be excellent.
@MFernflower Yes, let me know your opinion about the following Givaudan compounds (terpenoid-type compounds and aromatic compounds related to cinnamaldehyde): Ambrettolide Bisabolene Caryophyllenol Cinnamyl cinnamate Dupical Ebanol Ethyl safranate Florhydral Florocyclene Folenox Givescone Glycolierral Isolongifolanone cis-Jasmone Javanol Okoumal Oxyoctaline formate Safranal Silvial Spirambrene Spirogalbanone Verdoracine Vetyvenal

[MFernflower]

@bebi78 indeed those look promising although I wasn't expecting Silvial to look so much like ibuprofen!

I have not gotten a response from Firmenich yet as of writing this message

[MFernflower]

@wwjvdsande the compounds I want to get samples of from Firmenich are solids with a rather low melting point - could just fridge them if they melt during shipping maybe??

I am a few days into sending the message - no response yet from Firmenich - maybe @bebi78 or @mattodd can send one over - example letter to them is in this repository - Maybe I used wrong email or something?!?

[bebi78]

@MFernflower I called Givaudan Germany and they will discuss our request for their compounds. They will reply soon. Of course, I will contact them again in case there is a delay. I also called Firmenich Germany today and also wait now for their decision if they can provide us with Calone 1951, Habanolide and Scentenal.

[MFernflower]

@bebi78 I had changed over some of the requested compounds from Firmenich since there was some overlap with the ones you were requesting from Givaudan (compare Scentenal and Dupical for example)

Hopefully this won't be a problem!

Revised Firmenich Request List:

Calone Cascalone Civetone Cyclopentadecanone Doremox

[bebi78]

@MFernflower OK, I corrected the list of compounds for Firmenich and sent it to them by email. I will call them and Givaudan on Monday again.

[MFernflower]

@bebi78 Thanks for keeping up on this - I wonder if my email to Firmenich got stuck in a spam filter somewhere?

[bebi78]

@MFernflower I called them today again and both Firmenich and Givaudan told me it will take some days until they can give me a response, but they promised to do so.

[MFernflower]

Since we haven't yet gotten any information back from Firmenich @dmitrij176 maybe could possibly consider making a calone type compound? Maybe one without the methyl group?

[bebi78]

@MFernflower I haven't received an answer from Firmenich, yet, either. Givaudan forwarded me to IES-Ingredients in France. I hope they are cooperative.

[MFernflower]

@bebi78 A company located around 2 hour's from wendy's lab does sell a few interesting compounds including the calone and ambretolide

https://eng.hekserij.nl/

[MFernflower]

IES-Ingredients is the retail and distribution arm of Givaudan from what I have gathered @bebi78

[bebi78]

@MFernflower Thanks for the info. De Hekserej seems to be a very promising alternative supplier in NL. Prices are OK. But it also delivers only upon advance payment unless there is a special written agreement. Maybe we can conclude such an agreement. I will check their offered compounds this weekend more carefully if there are further interesting compounds in addition to calone and ambrettolide. I hope their products are OK and no witchcraft/hekserij/Hexerei :-)

[MFernflower]

@bebi78 A few interesting compounds from the site to point you in the right direction - Picona (a terpenoid from pine trees maybe?) and Zenolide (an ambrettolide analogue)

[bebi78]

@MFernflower OK, I have made the following list of possible interesting compounds by De Hekserij (top ones above the line are those also offered by Firmenich and Givaudan from our previous lists): Ambrettolide: 12 Euro, 10 ml Bisabolene: not in pure form, only as component of lime oil or black pepper oil Calone: 12.95 Euro, 10 g Cinnamyl cinnamate: not in pure form, only as component of Davana essential oil Ebanol: 5.95 Euro, 10 ml Ethyl safranate: 9.95 Euro, 5 g Florhydral: 6.95 Euro, 10 ml Isolongifolanone/Piconia: 4.95 Euro, 10 ml Javanol: 6.95 Euro, 1 g Safranal: 12.95 Euro, 10 ml Scentenal: 5.95 Euro, 10 ml

Bourgeonal: 7.95 Euro, 10 ml Cedroxyde: 5.95 Euro, 10 ml Damascone beta: 12.95 Euro, 10 ml (antifungal) Dihydrojasmone: 7.95 Euro, 10 ml (antifungal) Floralozone: 3.95 Euro, 10 ml Hexyl cinnamal: 4.95 Euro, 10 ml Isoeugenol: 5.95 Euro, 10 ml (antifungal) Methyl isoeugenol: 5 Euro, 10 ml (antifungal) Raspberry ketone: 3.95 Euro, 10 g (antifungal) Sandalore: 6 Euro, 10 ml Vetiveryl acetate: 12.95 Euro, 5 g Zenolide: 3.95 Euro, 10 ml

[bebi78]

@MFernflower A person from IES contacted me today afternoon. Unfortunately my mail to IES was truncated during the forwarding process and he did not know what compounds we want. So I had to write him our wishlist again this afternoon. I hope that I will get a positive answer from them next week.

[bebi78]

@MFernflower We will see whether IES-Givaudan will provide the requested compounds or at least some of them. But at least I'm in contact now with the expert person of IES-Givaudan who deals with such affairs and hope to make an agreement with him.

[MFernflower]

@bebi78 Sounds good!!! Hopefully IES-Givaudan will be interested in our project!

Maybe @wwjvdsande or @MA-Jjingyi could try to reach out to De Hekserij by phone or email https://hekserij.nl/contact/ to see what they can do about the four compounds since they are an under 2 hour drive away from Wendy's laboratory!

(these are the smallest sizes found on the website - maybe if we only ask for like 2 ml of the liquids and a 1/2 gram of the calone powder maybe they could work something out money wise?)

Zenolide: 3.95 Euro, 10 ml Calone: 12.95 Euro, 10 g Cedroxyde: 5.95 Euro, 10 ml Scentenal: 5.95 Euro, 10 ml

[MFernflower]

@bebi78 has any progress been made

[bebi78]

@MFernflower Yes, tonight my contact person from IES-Ingredients answered (see attached files) and he agreed to send the requested compounds for 5 Euros each (for 5 g), in total 115 Euros for the 23 selected compounds. As far as I can see advance payment is not required and payment can be carried out upon delivery of the package. I will establish an account for my university and order the compounds then on Monday. I hope it will work this time.

IES-Ingredients.docx Informations création compte client export-A.pdf

[MFernflower]

That leaves the 4 or so compounds from the Dutch chemical supplier we mentioned previous @wwjvdsande

https://hekserij.nl/contact/

[bebi78]

@MFernflower @wwjvdsande Yes, these are the four compounds IES does not offer. Personally, I also think hexyl cinnamal might be an interesting alternative or additive for Wendy's published CIN-102 mixture based on more than 80% cinnamaldehyde.

[MFernflower]

@bebi78 It's pretty interesting but not unexpected that crude drug research and aromachemical research overlap but then again humans have only recently developed fully synthetic fragrances in the last 150 years or so

[MFernflower]

@bebi78 Do you know if it's possible for them to include the molecular weights on the bottles

[bebi78]

@MFernflower Thanks. Seems that the order was successful this time. After receiving the package, I will prepare a package for Wendy and will care that the proper information will be placed in the package. I think the description of my samples was not the problem last time anyway since they were quickly tested in the lab. Because I expect to get 5 g of each sample there will be enough for chemical modifications, and I can send some grams to chemists of the group if there is interest.

[mattodd]

Hi - just catching up on this thread, which is now quite long! Could @MFernflower or @bebi78 consider summarising where we're up to in the wiki for this repo, in just a few lines of rationale and progress? The compounds that have been ordered - are they the ones that have been added to the Master List? i.e. is the compound list the same as for the first (unsuccessful order)? If not, we should fix. Out of interest, why is "adjuvant" used in the name of this repository? Aren't these compounds being evaluated for their ability to kill the pathogen, not to enhance an immune response?

[MFernflower]

With regards to the adjuvant name this was picked because the paper on the original paper Wendy and Mickey wrote 10.1371/journal.pntd.0009488 - had said the original product CIN-102 was a synergist

As to the general rationale - me and @bebi78 saw that since cin-102 was derived from an herbal remedy that we might as well look around that space (most synthetic perfume ingredients are analogues of chemicals isolated from herbs)

@mattodd

[MFernflower]

I think once we get some decent data for in-vivo and in-vitro screening of the plant extracts from Africa, the listed above aroma-chemicals and the natural product derivatives from @bebi78

We could perhaps package all of that data into a short paper perhaps using the connective tissue of these products being either herbal or derivatives/analogues of herbal products - An example paper title I just came up with out of the top of my head:

"Tapping the perfume tree: Diverse isolates and analogues of plant natural products show activity against eumycetoma causing fungi"

Thoughts @OpenSourceMycetoma/corecontrib ???????

[wwjvdsande]

@OpenSourceMycetoma/corecontrib @MFernflower @bebi78 sounds good. It does depend a bit on how many compounds we have to screen this year on all compounds series in the larvae if it is doable of course. At the moment it is still to cold here to start last week we still had snow. We are aiming to start the first week of may this year.

[MFernflower]

@bebi78 did the compounds arrive??