[qw098]

Hi Guys,

I was wondering what does it mean in synthesis when it says "longest linear sequence"?

When synthesizing a compound... don't you have many steps/sequences, but what is meant by "longest linear sequence" specifically when determining things such as percent yield and possible yield.

Any help would be appreciated, thanks!

[Doc Oc]

Suppose you're making a molecule.  You decide that the best way to do it is break it in half, make the two halves separately, then combine them at the end.  One half of the molecule takes 5 steps to make, the other takes 7.  Then when you have them it takes 3 more steps to get them together.  If you start from the half that took 5 steps, it's 8 total steps to completion.  If you start from the half that takes 7 steps, it's 10 total steps to completion.  So 10 steps is the longest linear sequence, the 5 steps necessary to make the other half don't count towards that.

[qw098]

I find the longest linear sequence method a ridiculous way to determine how much of a starting compound you would need to synthesize a final compound.

Imagine you want to make compound B from compound A. You need to break compound A into two and then build your compound. One half of compound A took 7 steps, while the other took 5 steps. To join these compounds it then takes three steps. Like you said earlier, my longest linear sequence would be 10.

So, let's say I wanted to make 10g of the compound B, how many grams of compound A would I need if after each step I only get a 90% yield? I would simply do: 10g/(0.9^10) which would give me 28.7g. This would mean I would need 28.7g of the starting material to reach 10g of compound B.

Don't you mind it ridiculous I must use the longest linear sequence to determine how much starting material I would need? It doesn't make much sense at all... Why wouldn't I include the other 5 steps I needed to make the other half of the molecule...?

[discodermolide]

I find the longest linear sequence method a ridiculous way to determine how much of a starting compound you would need to synthesize a final compound.

Imagine you want to make compound B from compound A. You need to break compound A into two and then build your compound. One half of compound A took 7 steps, while the other took 5 steps. To join these compounds it then takes three steps. Like you said earlier, my longest linear sequence would be 10.

So, let's say I wanted to make 10g of the compound B, how many grams of compound A would I need if after each step I only get a 90% yield? I would simply do: 10g/(0.9^10) which would give me 28.7g. This would mean I would need 28.7g of the starting material to reach 10g of compound B.

What other way do you suggest?
Take a look at some long natural product syntheses, e.g. discodermolide and work out how much Roche ester you would need to make 1Kg. Excel is a good tool to use. The longest linear sequence here is 27 steps. Examine other possibilities.

Don't you mind it ridiculous I must use the longest linear sequence to determine how much starting material I would need? It doesn't make much sense at all... Why wouldn't I include the other 5 steps I needed to make the other half of the molecule...?

[discodermolide]

Take a look at some long natural product syntheses, e.g. discodermolide and work out how much Roche ester you would need to make 1Kg. Excel is a good tool to use. The longest linear sequence here is 27 steps. Examine other possibilities.
Byrostatin 19 is another good example, or halichondrin.
Tip, identify what you think is the longest linear sequence and work backwards to your starting material.

[qw098]

Nice, good stuff, thanks