So, let's say that some jungle-extract natural product has shown good activity in some drug screens. What next?
The first thing to do is define "good activity". Screens can be done at several levels. The most abstract is against a purified protein (enzyme inhibition, for example), and that can be a long way from anything useful in a living system. You'd get excited if you have activity against an enzyme that a lot of people are interested in but no one's been able to get good activity against - protein tyrosine phosphatase 1B, for example, a fine diabetes target that's evaded all attempts so far at useful small-molecule inhibition.
A more stringent test is against living cells. Activity there shows you that you at least can deal with cell membranes (penetrating them or hitting targets on their surface) and that you can get the desired effect in the presence of all the other potential binding sites that a living system presents. Cancer assays are often done with living tumor cells, with the readout being slowed growth or outright cell death. (That latter one isn't as good as it might sound, since most things that will kill cancerous cells will kill every other kind of cell, too).
But let's assume that this natural product has shown something that's really worth following up. You're going to need more of it for animal models and toxicity testing. Now comes a tough decision: make the compound, or extract it? The former is often out of the question, since many of the structures we're talking about are so complex. Academic groups make them, of course, for the sheer challenge of it, and often talk about how their routes have opened up new possibilities for analogs of the original compound. But how often does that really happen? No one's going to do med-chem analoging in the context of a thirty-step synthesis.
The back-to-nature option isn't always available, either. Most natural products are found in such low concentation that insane amounts of the source material would be needed. In other cases, particularly with marine natural products, the source organism may have disappeared from its original collection site over the years. Some of these things have never been found again.
The most successful natural product drugs have been those that have a high-volume plant source somewhere in their pipeline. The Vinca alkaloids, for example, come from the fast-growing Madagascar periwinkle. (You could say the same thing about opium and cocaine, too, I guess, which have been successful in their way). You can't always find a good source of the final compound, though.
The next best thing is to find an advanced intermediate that a plant produces in quantity. That's the foundation for the modern steroid industry - it turned out that you could have Mexican yams make most of the steroid backbone for you, which is a wild story that's been told many times. A more recent example is taxol. Extracting the final compound from the Pacific yew tree just wasn't feasible on scale, not least because it was found in the bark and couldn't be obtained without killing the trees. Folks were looking at a yield of about a half-gram of drug per forty-foot tree - mind you, that's still easier than making the compound from scratch. But an advanced intermediate could be extracted from the needles, and Holton's group worked out a synthetic route from it.
Actually, those semisynthetic route might be the best overall, because it gives you a handle to generate analogs (the way the total synthesis routes do, in theory). Natural products are rarely given the kind of exhaustive structure-activity workout that smaller man-made molecues get - or if they do get one, it takes years to slowly work through the possibilities. You won't be able to ring all the changes based on what you get from the plant, but it's better than nothing. Taxol, for example, has had a great deal of work done on it, mostly in attempts to make the damn stuff more soluble. As it is, it has to be dosed in a vehicle that's almost worse than the drug for toxicity. That's a cruel trick of Nature, all right - insoluble compounds are something we can make on our own.